2021/07/12 更新

写真a

サカモト ヒロタカ
坂本 浩隆
SAKAMOTO Hirotaka
所属
自然科学学域 准教授
職名
准教授
外部リンク

学位

  • 博士(医学) ( 京都府立医科大学 )

  • 博士(学術) ( 広島大学 )

研究キーワード

  • neuroendocrinology

  • stress

  • 内分泌

  • 神経

  • 解剖

研究分野

  • ライフサイエンス / 神経科学一般

  • ライフサイエンス / 神経科学一般

  • ライフサイエンス / 神経形態学

  • ライフサイエンス / 形態、構造

学歴

  • 広島大学   大学院生物圏科学研究科 (修了) 博士(学術)  

    1997年4月 - 2002年3月

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    国名: 日本国

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  • 広島大学   生物生産学部(卒業)  

    1994年4月 - 1997年3月

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    国名: 日本国

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  • 京都府立医科大学   大学院医学研究科 博士(医学)  

    2009年3月

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経歴

  • - 岡山大学自然科学研究科 准教授

    2009年 - 現在

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  • - 京都府立医科大学大学院 医学研究科 客員講師(併任) 客員講師

    2009年

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  • 京都府立医科大学大学院医学研究科 助教   Graduate School of Medical Science

    2007年 - 2009年

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  • 京都府立医科大学大学院医学研究科 助手   Graduate School of Medical Science

    2003年 - 2007年

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  • 日本学術振興会特別研究員 日本学術振興会特別研究員

    2001年 - 2003年

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所属学協会

▼全件表示

委員歴

  • 日本神経内分泌学会   評議委員  

    2010年   

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    団体区分:学協会

    日本神経内分泌学会

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  • 日本動物学会   中国四国支部企画委員  

    2009年   

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    団体区分:学協会

    日本動物学会

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論文

  • Variation of pro-vasopressin processing in parvocellular and magnocellular neurons in the paraventricular nucleus of the hypothalamus: Evidence from the vasopressin-related glycopeptide copeptin. 査読 国際誌

    Natsuko Kawakami, Akito Otubo, Sho Maejima, Ashraf H Talukder, Keita Satoh, Takumi Oti, Keiko Takanami, Yasumasa Ueda, Keiichi Itoi, John F Morris, Tatsuya Sakamoto, Hirotaka Sakamoto*

    The Journal of Comparative Neurology   529 ( 7 )   1372 - 1390   2021年5月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Arginine vasopressin (AVP) is synthesized in parvocellular- and magnocellular neuroendocrine neurons in the paraventricular nucleus (PVN) of the hypothalamus. Whereas magnocellular AVP neurons project primarily to the posterior pituitary, parvocellular AVP neurons project to the median eminence (ME) and to extrahypothalamic areas. The AVP gene encodes pre-pro-AVP that comprises the signal peptide, AVP, neurophysin (NPII), and a copeptin glycopeptide. In the present study, we used an N-terminal copeptin antiserum to examine copeptin expression in magnocellular and parvocellular neurons in the hypothalamus in the mouse, rat, and macaque monkey. Although magnocellular NPII-expressing neurons exhibited strong N-terminal copeptin immunoreactivity in all three species, a great majority (~90%) of parvocellular neurons that expressed NPII was devoid of copeptin immunoreactivity in the mouse, and in approximately half (~53%) of them in the rat, whereas in monkey hypothalamus, virtually all NPII-immunoreactive parvocellular neurons contained strong copeptin immunoreactivity. Immunoelectron microscopy in the mouse clearly showed copeptin-immunoreactivity co-localized with NPII-immunoreactivity in neurosecretory vesicles in the internal layer of the ME and posterior pituitary, but not in the external layer of the ME. Intracerebroventricular administration of a prohormone convertase inhibitor, hexa-d-arginine amide resulted in a marked reduction of copeptin-immunoreactivity in the NPII-immunoreactive magnocellular PVN neurons in the mouse, suggesting that low protease activity and incomplete processing of pro-AVP could explain the disproportionally low levels of N-terminal copeptin expression in rodent AVP (NPII)-expressing parvocellular neurons. Physiologic and phylogenetic aspects of copeptin expression among neuroendocrine neurons require further exploration.

    DOI: 10.1002/cne.25026

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  • In vivo electrophysiology of peptidergic neurons in deep layers of the lumbar spinal cord after optogenetic stimulation of hypothalamic paraventricular oxytocin neurons in rats. 査読 国際誌

    Daisuke Uta*, Takumi Oti, Tatsuya Sakamoto, Hirotaka Sakamoto*

    International Journal of Molecular Sciences   22 ( 7 )   2021年3月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The spinal ejaculation generator (SEG) is located in the central gray (lamina X) of the rat lumbar spinal cord and plays a pivotal role in the ejaculatory reflex. We recently reported that SEG neurons express the oxytocin receptor and are activated by oxytocin projections from the paraventricular nucleus of hypothalamus (PVH). However, it is unknown whether the SEG responds to oxytocin in vivo. In this study, we analyzed the characteristics of the brain-spinal cord neural circuit that controls male sexual function using a newly developed in vivo electrophysiological technique. Optogenetic stimulation of the PVH of rats expressing channel rhodopsin under the oxytocin receptor promoter increased the spontaneous firing of most lamina X SEG neurons. This is the first demonstration of the in vivo electrical response from the deeper (lamina X) neurons in the spinal cord. Furthermore, we succeeded in the in vivo whole-cell recordings of lamina X neurons. In vivo whole-cell recordings may reveal the features of lamina X SEG neurons, including differences in neurotransmitters and response to stimulation. Taken together, these results suggest that in vivo electrophysiological stimulation can elucidate the neurophysiological response of a variety of spinal neurons during male sexual behavior.

    DOI: 10.3390/ijms22073400

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  • Oxytocin influences male sexual activity via non-synaptic axonal release in the spinal cord 査読

    Takumi Oti, Keita Satoh, Daisuke Uta, Junta Nagafuchi, Sayaka Tateishi, Ryota Ueda, Keiko Takanami, Larry J. Young, Antony Galione, John F. Morris, Tatsuya Sakamoto, Hirotaka Sakamoto*

    Current Biology   31 ( 1 )   103 - 114.e5   2021年1月

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.cub.2020.09.089

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  • Spinal astrocytes in superficial laminae gate brainstem descending control of mechanosensory hypersensitivity 査読

    Yuta Kohro, Tsuyoshi Matsuda, Kohei Yoshihara, Keita Kohno, Keisuke Koga, Ryuichi Katsuragi, Takaaki Oka, Ryoichi Tashima, Sho Muneta, Takuya Yamane, Shota Okada, Kazuya Momokino, Aogu Furusho, Kenji Hamase, Takumi Oti, Hirotaka Sakamoto, Kenichiro Hayashida, Ryosuke Kobayashi, Takuro Horii, Izuho Hatada, Hidetoshi Tozaki-Saitoh, Katsuhiko Mikoshiba, Verdon Taylor, Kazuhide Inoue, Makoto Tsuda

    Nature Neuroscience   23 ( 11 )   1376 - 1387   2020年11月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1038/s41593-020-00713-4

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    その他リンク: http://www.nature.com/articles/s41593-020-00713-4

  • Degradation of mutant protein aggregates within the endoplasmic reticulum of vasopressin neurons. 査読 国際誌

    Takashi Miyata, Daisuke Hagiwara, Yuichi Hodai, Tsutomu Miwata, Yohei Kawaguchi, Junki Kurimoto, Hajime Ozaki, Kazuki Mitsumoto, Hiroshi Takagi, Hidetaka Suga, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Yoshihiro Ito, Shintaro Iwama, Ryoichi Banno, Mami Matsumoto, Natsuko Kawakami, Nobuhiko Ohno, Hirotaka Sakamoto, Hiroshi Arima

    iScience   23 ( 10 )   101648 - 101648   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Misfolded or unfolded proteins in the ER are said to be degraded only after translocation or isolation from the ER. Here, we describe a mechanism by which mutant proteins are degraded within the ER. Aggregates of mutant arginine vasopressin (AVP) precursor were confined to ER-associated compartments (ERACs) connected to the ER in AVP neurons of a mouse model of familial neurohypophysial diabetes insipidus. The ERACs were enclosed by membranes, an ER chaperone and marker protein of phagophores and autophagosomes were expressed around the aggregates, and lysosomes fused with the ERACs. Moreover, lysosome-related molecules were present within the ERACs, and aggregate degradation within the ERACs was dependent on autophagic-lysosomal activity. Thus, we demonstrate that protein aggregates can be degraded by autophagic-lysosomal machinery within specialized compartments of the ER.

    DOI: 10.1016/j.isci.2020.101648

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  • Vasopressin gene products are colocalised with corticotrophin-releasing factor within neurosecretory vesicles in the external zone of the median eminence of the Japanese macaque monkey (Macaca fuscata). 査読 国際誌

    Akito Otubo, Natsuko Kawakami, Sho Maejima, Yasumasa Ueda, John F Morris, Tatsuya Sakamoto, Hirotaka Sakamoto*

    Journal of Neuroendocrinology   32 ( 8 )   e12875   2020年8月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Arginine vasopressin (AVP), when released into portal capillaries with corticotrophin-releasing factor (CRF) from terminals of parvocellular neurones of the hypothalamic paraventricular nucleus (PVH), facilitates the secretion of adrenocorticotrophic hormone (ACTH) in stressed rodents. The AVP gene encodes a propeptide precursor containing AVP, AVP-associated neurophysin II (NPII), and a glycopeptide copeptin, although it is currently unclear whether copeptin is always cleaved from the neurophysin and whether the NPII and/or copeptin have any functional role in the pituitary. Furthermore, for primates, it is unknown whether CRF, AVP, NPII and copeptin are all colocalised in neurosecretory vesicles in the terminal region of the paraventricular CRF neurone axons. Therefore, we investigated, by fluorescence and immunogold immunocytochemistry, the cellular and subcellular relationships of these peptides in the CRF- and AVP-producing cells in unstressed Japanese macaque monkeys (Macaca fuscata). Reverse transcription-polymerase chain reaction analysis showed the expression of both CRF and AVP mRNAs in the monkey PVH. As expected, in the magnocellular neurones of the PVH and supraoptic nucleus, essentially no CRF immunoreactivity could be detected in NPII-immunoreactive (AVP-producing) neurones. Immunofluorescence showed that, in the parvocellular part of the PVH, NPII was detectable in a subpopulation (approximately 39%) of the numerous CRF-immunoreactive neuronal perikarya, whereas, in the outer median eminence, NPII was more prominent (approximately 52%) in the CRF varicosities. Triple immunoelectron microscopy in the median eminence demonstrated the presence of both NPII and copeptin immunoreactivity in dense-cored vesicles of CRF-containing axons. The results are consistent with an idea that the AVP propeptide is processed and NPII and copeptin are colocalised in hypothalamic-pituitary CRF axons in the median eminence of a primate. The CRF, AVP and copeptin are all co-packaged in neurosecretory vesicles in monkeys and are thus likely to be co-released into the portal capillary blood to amplify ACTH release from the primate anterior pituitary.

    DOI: 10.1111/jne.12875

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  • Effects of Sex Steroids on the Spinal Gastrin-Releasing Peptide System Controlling Male Sexual Function in Rats 査読

    Takumi Oti, Keiko Takanami, Saya Ito, Takashi Ueda, Ken Ichi Matsuda, Mitsuhiro Kawata, Jintetsu Soh, Osamu Ukimura, Tatsuya Sakamoto, Hirotaka Sakamoto*

    Endocrinology   159 ( 4 )   1886 - 1896   2018年4月

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    担当区分:最終著者, 責任著者   掲載種別:研究論文(学術雑誌)   出版者・発行元:The Endocrine Society  

    DOI: 10.1210/en.2018-00043

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  • Nemertean and phoronid genomes reveal lophotrochozoan evolution and the origin of bilaterian heads 査読

    Yi-Jyun Luo, Miyuki Kanda, Ryo Koyanagi, Kanako Hisata, Tadashi Akiyama, Hirotaka Sakamoto, Tatsuya Sakamoto, Noriyuki Satoh

    Nature Ecology and Evolution   2 ( 1 )   141 - 151   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    Nemerteans (ribbon worms) and phoronids (horseshoe worms) are closely related lophotrochozoans - a group of animals including leeches, snails and other invertebrates. Lophotrochozoans represent a superphylum that is crucial to our understanding of bilaterian evolution. However, given the inconsistency of molecular and morphological data for these groups, their origins have been unclear. Here, we present draft genomes of the nemertean Notospermus geniculatus and the phoronid Phoronis australis, together with transcriptomes along the adult bodies. Our genome-based phylogenetic analyses place Nemertea sister to the group containing Phoronida and Brachiopoda. We show that lophotrochozoans share many gene families with deuterostomes, suggesting that these two groups retain a core bilaterian gene repertoire that ecdysozoans (for example, flies and nematodes) and platyzoans (for example, flatworms and rotifers) do not. Comparative transcriptomics demonstrates that lophophores of phoronids and brachiopods are similar not only morphologically, but also at the molecular level. Despite dissimilar head structures, lophophores express vertebrate head and neuronal marker genes. This finding suggests a common origin of bilaterian head patterning, although different heads evolved independently in each lineage. Furthermore, we observe lineage-specific expansions of innate immunity and toxin-related genes. Together, our study reveals a dual nature of lophotrochozoans, where conserved and lineage-specific features shape their evolution.

    DOI: 10.1038/s41559-017-0389-y

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    その他リンク: http://orcid.org/0000-0002-6224-4591

  • A sexually dimorphic peptidergic system in the lower spinal cord controlling penile function in non-human primates 査読

    T. Ito, T. Oti, K. Takanami, K. Satoh, Y. Ueda, T. Sakamoto, H. Sakamoto

    Spinal Cord   56 ( 1 )   57 - 62   2018年

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Nature Publishing Group  

    Study design: Experimental animal study. Objectives: Although a population of gastrin-releasing peptide (GRP) neurons in the lumbar spinal cord has an important role in erection and ejaculation in rats, little information exists on this GRP system in primates. To identify the male-specific GRP system in the primate spinal cord, we studied the lumbosacral cord in macaque monkeys as a non-human primate model. Setting: University laboratory in Japan. Methods: To determine the gene sequence of GRP precursors, the rhesus macaque monkey genomic sequence data were searched, followed by phylogenetic analysis. Subsequently, immunocytochemical analysis for GRP was performed in the monkey spinal cord. Results: We have used bioinformatics to identify the ortholog gene for GRP precursor in macaque monkeys. Phylogenetic analysis suggested that primate prepro-GRP is separated from that of other mammalian species and clustered to an independent branch as primates. Immunocytochemistry for GRP further demonstrated that male-dominant sexual dimorphism was found in the spinal GRP system in monkeys as in rodents. Conclusion: We have demonstrated in macaque monkeys that the GRP system in the lower spinal cord shows male-specific dimorphism and May have an important role in penile functions not only in rodents but also in primates.

    DOI: 10.1038/sc.2017.105

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    その他リンク: http://orcid.org/0000-0002-6224-4591

  • Activation of supraoptic oxytocin neurons by secretin facilitates social recognition. 査読 国際誌

    Yuki Takayanagi, Masahide Yoshida, Akihide Takashima, Keiko Takanami, Shoma Yoshida, Katsuhiko Nishimori, Ichiko Nishijima, Hirotaka Sakamoto, Takanori Yamagata, Tatsushi Onaka

    Biological Psychiatry   81 ( 3 )   243 - 251   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE INC  

    BACKGROUND: Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. METHODS: Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. RESULTS: Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. CONCLUSIONS: The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits.

    DOI: 10.1016/j.biopsych.2015.11.021

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    その他リンク: http://orcid.org/0000-0002-6224-4591

  • Perinatal testosterone exposure is critical for the development of the male-specific sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that mediates erection and ejaculation 査読

    Takumi Oti, Keiko Takanami, Nao Katayama, Tomoca Edey, Keita Satoh, Tatsuya Sakamoto, Hirotaka Sakamoto*

    BIOLOGY OF SEX DIFFERENCES   7 ( 1 )   4   2016年1月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMED CENTRAL LTD  

    Background: In rats, a sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord projects to spinal centers that control erection and ejaculation. This system controls the sexual function of adult males in an androgen-dependent manner. In the present study, we assessed the influence of androgen exposure on the spinal GRP system during a critical period of the development of sexual dimorphism.
    Methods: Immunohistochemistry was used to determine if the development of the spinal GRP system is regulated by the perinatal androgen surge. We first analyzed the responses of neonates administered with anti-androgen flutamide. To remove endogenous androgens, rats were castrated at birth. Further, neonatal females were administered androgens during a critical period to evaluate the development of the male-specific spinal GRP system.
    Results: Treatment of neonates with flutamide on postnatal days 0 and 1 attenuated the spinal GRP system during adulthood. Castrating male rats at birth resulted in a decrease in the number of GRP neurons and the intensity of neuronal GRP in the spinal cord during adulthood despite testosterone supplementation during puberty. This effect was prevented if the rats were treated with testosterone propionate immediately after castration. Moreover, treating female rats with androgens on the day of birth and the next day, masculinized the spinal GRP system during adulthood, which resembled the masculinized phenotype of adult males and induced a hypermasculine appearance.
    Conclusions: The perinatal androgen surge plays a key role in masculinization of the spinal GRP system that controls male sexual behavior. Further, the present study provides potentially new approaches to treat sexual disorders of males.

    DOI: 10.1186/s13293-016-0058-x

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  • In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS. 査読 国際誌

    Yuji Takihara, Masaru Inatani, Kei Eto, Toshihiro Inoue, Alexander Kreymerman, Seiji Miyake, Shinji Ueno, Masatoshi Nagaya, Ayami Nakanishi, Keiichiro Iwao, Yoshihiro Takamura, Hirotaka Sakamoto, Keita Satoh, Mineo Kondo, Tatsuya Sakamoto, Jeffrey L Goldberg, Junichi Nabekura, Hidenobu Tanihara

    Proceedings of the National Academy of Sciences of the United States of America   112 ( 33 )   10515 - 20   2015年8月

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    記述言語:英語  

    The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23-25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.

    DOI: 10.1073/pnas.1509879112

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  • In vivo processing and release into the circulation of GFP fusion protein in arginine vasopressin enhanced GFP transgenic rats: response to osmotic stimulation 査読

    Keita Satoh, Takumi Oti, Akiko Katoh, Yoichi Ueta, John F. Morris, Tatsuya Sakamoto, Hirotaka Sakamoto*

    FEBS JOURNAL   282 ( 13 )   2488 - 2499   2015年7月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Arginine vasopressin (AVP) is a neurohypophysial hormone synthesized as a part of a prepropeptide precursor containing the signal peptide, AVP hormone, AVP-associated neurophysin II and copeptin in the hypothalamic neurosecretory neurons. A transgenic (Tg) rat line expressing the AVP-eGFP fusion gene has been generated. To establish the AVP-eGFP Tg rat as a unique model for an analysis of AVP dynamics invivo, we first examined the invivo molecular dynamics of the AVP-eGFP fusion gene, and then the release of GFP in response to physiological stimuli. Double immunoelectron microscopy demonstrated that GFP was specifically localized in neurosecretory vesicles of AVP neurons in this Tg rat. After stimulation of the posterior pituitary with high potassium we demonstrated the exocytosis of AVP neurosecretory vesicles containing GFP at the ultrastructural level. Biochemical analyses indicated that the AVP-eGFP fusion gene is subjected to invivo post-translational modifications like the native AVP gene, and is packaged into neurosecretory vesicles as a fusion protein: copeptin(1-14)-GFP. Moreover, GFP release into the circulating blood appeared to be augmented after osmotic stimulation, like native AVP. Thus, here we show for the first time the invivo molecular processing of the AVP-eGFP fusion gene and stimulated secretion after osmotic stimulation in rats. Because GFP behaved like native AVP in the hypothalamo-pituitary axis, and in particular was released into the circulation in response to a physiological stimulus, the AVP-eGFP Tg rat model appears to be a powerful tool for analyzing neuroendocrine systems at the organismal level.

    DOI: 10.1111/febs.13291

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  • Androgen regulates the sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord that mediates male sexual function 査読

    Hirotaka Sakamoto*, Keiko Takanami, Damian G. Zuloaga, Ken-ichi Matsuda, Cynthia L. Jordan, S. Marc Breedlove, Mitsuhiro Kawata

    ENDOCRINOLOGY   150 ( 8 )   3672 - 3679   2009年8月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ENDOCRINE SOC  

    A collection of neurons in the upper lumbar spinal cord of male rats projects to the lower lumbar spinal cord, releasing gastrin-releasing peptide (GRP) onto somatic and autonomic centers known to regulate male sexual reflexes such as erection and ejaculation. Because these reflexes are androgen dependent, we asked whether manipulating levels of androgen in adult rats would affect GRP expression in this spinal center. We found that castration resulted, 28 d later, in a profound decrease in the expression of GRP in the spinal cord, as reflected in immunocytochemistry and competitive ELISA for the protein as well as real-time quantitative PCR for the transcript. These effects were prevented if the castrates were treated with testosterone propionate. Genetically male (XY) rats with the dysfunctional testicular feminization allele for the androgen receptor (AR) displayed GRP mRNA and protein levels in the spinal cord similar to those of females, indicating that androgen normally maintains the system through AR. We saw no effect of castration or the testicular feminization allele on expression of the receptor for GRP in the spinal cord, but castration did reduce expression of AR transcripts within the spinal cord as revealed by real-time quantitative PCR and Western blots. Taken together, these results suggest that androgen signaling plays a pivotal role in the regulation of GRP expression in male lumbar spinal cord. A greater understanding of how androgen modulates the spinal GRP system might lead to new therapeutic approaches to male sexual dysfunction. (Endocrinology 150: 3672-3679, 2009)

    DOI: 10.1210/en.2008-1791

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  • Stress affects a gastrin-releasing peptide system in the spinal cord that mediates sexual function: Implications for psychogenic erectile dysfunction 査読

    Hirotaka Sakamoto*, Ken-Ichi Matsuda, Damian G. Zuloaga, Nobuko Nishiura, Keiko Takanami, Cynthia L. Jordan, S. Marc Breedlove, Mitsuhiro Kawata

    PLoS ONE   4 ( 1 )   e4276   2009年1月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    Background: Many men suffering from stress, including post-traumatic stress disorder (PTSD), report sexual dysfunction, which is traditionally treated via psychological counseling. Recently, we identified a gastrin-releasing peptide (GRP) system in the lumbar spinal cord that is a primary mediator for male reproductive functions.
    Methodology/Principal Findings: To ask whether an acute severe stress could alter the male specific GRP system, we used a single-prolonged stress (SPS), a putative rat model for PTSD in the present study. Exposure of SPS to male rats decreases both the local content and axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Remarkably, pharmacological stimulation of GRP receptors restores penile reflexes in SPS-exposed males, and induces spontaneous ejaculation in a dose-dependent manner. Furthermore, although the level of plasma testosterone is normal 7 days after SPS exposure, we found a significant decrease in the expression of androgen receptor protein in this spinal center.
    Conclusions/Significance: We conclude that the spinal GRP system appears to be a stress-vulnerable center for male reproductive functions, which may provide new insight into a clinical target for the treatment of erectile dysfunction triggered by stress and psychiatric disorders.

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  • Sexually dimorphic gastrin releasing peptide system in the spinal cord controls male reproductive functions 査読

    Hirotaka Sakamoto*, Ken-Ichi Matsuda, Damian G. Zuloaga, Hisayuki Hongu, Etsuko Wada, Keiji Wada, Cynthia L. Jordan, S. Marc Breedlove, Mitsuhiro Kawata

    Nature Neuroscience   11 ( 6 )   634 - 636   2008年6月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Neurons in the upper lumbar spinal cord project axons containing gastrin-releasing peptide (GRP) to innervate lower lumbar regions controlling erection and ejaculation. This system is vestigial in female rats and in males with genetic dysfunction of androgen receptors, but in male rats, pharmacological stimulation of spinal GRP receptors restores penile reflexes and ejaculation after castration. GRP offers new avenues for understanding potential therapeutic approaches to masculine reproductive dysfunction.

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  • Expression of G protein-coupled receptor-30, a g protein-coupled membrane estrogen receptor, in oxytocin neurons of the rat paraventricular and supraoptic nuclei 査読

    Hirotaka Sakamoto*, Ken-Ichi Matsuda, Koji Hosokawa, Mayumi Nishi, John F. Morris, Eric R. Prossnitz, Mitsuhiro Kawata

    ENDOCRINOLOGY   148 ( 12 )   5842 - 5850   2007年12月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ENDOCRINE SOC  

    The regulatory actions of estrogens on magnocellular oxytocin (OT) neurons of the paraventricular and supraoptic nuclei are well documented. Although the expression and distribution of nuclear estrogen receptor-beta, but not estrogen receptor-alpha, in the OT neuron has been described, the nuclear receptors may not explain all aspects of estrogen function in the hypothalamic OT neuron. Recently a G protein-coupled receptor (GPR) for estrogens, GPR30, has been identified as a membrane-localized estrogen receptor in several cancer cell lines. In this study, we therefore investigated the expression and localization of GPR30 in magnocellular OT neurons to understand the mode of rapid estrogen actions within these neurons. Here we show that, in the paraventricular nucleus and supraoptic nucleus, GPR30 is expressed in magnocellular OT neurons at both mRNA and protein levels but is not expressed in vasopressin neurons. Specific markers for intracellular organelles and immunoelectron microscopy revealed that GPR30 was localized mainly in the Golgi apparatus of the neurons but could not be detected at the cell surface. In addition, the expression of GPR30 is also detected in the neurohypophysis. These results suggest that GPR30 may serve primarily as a nongenomic transducer of estrogen actions in the hypothalamo-neurohypophyseal system.

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  • Systemic effects of oxytocin on male sexual activity via the spinal ejaculation generator in rats. 査読 国際誌

    Takumi Oti, Tatsuya Sakamoto, Hirotaka Sakamoto*

    Communicative & Integrative Biology   14 ( 1 )   55 - 60   2021年3月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Oxytocin is produced in the hypothalamus and stimulates uterine contraction and milk ejection. While many people consider oxytocin to be a female hormone, it is reported that, in men, the plasma oxytocin level increases markedly after ejaculation. However, this aspect of oxytocin physiology is poorly understood. The spinal ejaculation generator (SEG), which expresses the neuropeptide, gastrin-releasing peptide (GRP), can trigger ejaculation in rats. Therefore, we focused on systemic effects of oxytocin on the GRP/SEG neuron system in the lumbar spinal cord controlling sexual activity in male rats. We found that systemic administration of oxytocin significantly shortened the latency to the first mount, intromission and ejaculation during male copulatory behavior. In addition, the local oxytocin level in the lumbar cord was significantly higher in males than in females. Histological analysis showed that oxytocin-binding is apparent in spinal GRP/SEG neurons. We therefore conclude that oxytocin influences male sexual activity via the SEG.

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  • Metabotropic glutamate receptor subtype 7 is essential for ejaculation. 査読 国際誌

    Miwako Masugi-Tokita, Keiji Tomita, Kenichi Kobayashi, Tetsuya Yoshida, Susumu Kageyama, Hirotaka Sakamoto, Akihiro Kawauchi

    Molecular Neurobiology   57 ( 12 )   5208 - 5218   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localized to presynaptic active zones of the mammalian central nervous system (CNS). To elucidate the mechanism of impaired reproductivity of mGluR7 knockout (KO) mice, we investigated sexual behavior in this line, which exhibits ejaculatory disorder, although with normal sexual motivation and erectile function. To identify the site of action within the CNS responsible for the effect of mGluR7 on ejaculation, we then used a para-chloroamphetamine (PCA)-induced ejaculation model. Intrathecal administration of the mGluR7-selective antagonist 6-(4-methoxyphenyl)-5-methyl-3-pyridin-4-ylisoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP) into the lumbosacral spinal cord inhibited PCA-induced ejaculation. Immunohistochemistry revealed mGluR7-like immunoreactivity (LI) expressed in the same area where lumbar spinothalamic (LSt) cells regulate the parasympathetic ejaculatory pathway. At high magnification, the apposition of mGluR7-LI puncta and neuronal nitric oxide synthase (nNOS)-LI-positive putative parasympathetic preganglionic neurons was evident. These results indicate that mGluR7 in the lumbosacral spinal cord regulates ejaculation by potentiating the excitability of parasympathetic preganglionic neurons. The ejaculatory disorder is a major issue in the field of male reproductive function. Erectile dysfunction (ED) can be treated by phosphodiesterase type 5 inhibitors like sildenafil (Viagra®), but the ejaculatory disorder cannot. Lack of understanding of the ejaculatory mechanism hinders the development of therapies for ejaculatory problems. This study is the first to demonstrate that mGluR7 regulates ejaculation and the results provide insight into the mechanism of ejaculation as well as a strategy for future therapies to treat ejaculatory disorders in humans.

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  • Detection and characterization of estrogen receptor beta expression in the brain with newly developed transgenic mice. 査読 国際誌

    Shoko Sagoshi, Sho Maejima, Masahiro Morishita, Satoshi Takenawa, Akito Otubo, Keiko Takanami, Tatsuya Sakamoto, Hirotaka Sakamoto, Shinji Tsukahara, Sonoko Ogawa

    Neuroscience   438   182 - 197   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Two types of nuclear estrogen receptors, ERα and ERβ, have been shown to be differentially involved in the regulation of various types of behaviors. Due to a lack of tools for identifying ERβ expression, detailed anatomical distribution and neurochemical characteristics of ERβ expressing cells and cellular co-expression with ERα remain unclear. We have generated transgenic mice ERβ-RFPtg, in which RFP was inserted downstream of ERβ BAC promotor. We verified RFP signals as ERβ by confirming: (1) high ERβ mRNA levels in RFP-expressing cells collected by fluorescence-activated cell sorting; and (2) co-localization of ERβ mRNA and RFP proteins in the paraventricular nucleus (PVN). Strong ERβ-RFP signals were found in the PVN, medial preoptic area (MPOA), bed nucleus of the stria terminalis, medial amygdala (MeA), and dorsal raphe nucleus (DRN). In the MPOA and MeA, three types of cell populations were identified; those expressing both ERα and ERβ, and those expressing exclusively either ERα or ERβ. The majority of PVN and DRN cells expressed only ERβ-RFP. Further, ERβ-RFP positive cells co-expressed oxytocin in the PVN, and tryptophan hydroxylase 2 and progesterone receptors in the DRN. In the MeA, some ERβ-RFP positive cells co-expressed oxytocin receptors. These findings collectively suggest that ERβ-RFPtg mice can be a powerful tool for future studies on ERβ function in the estrogenic regulation of social behaviors.

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  • The phosphatidylcholine transfer protein StarD7 is important for myogenic differentiation in mouse myoblast C2C12 cells and human primary skeletal myoblasts. 査読 国際誌

    Yasuhiro Horibata, Satomi Mitsuhashi, Hiroaki Shimizu, Sho Maejima, Hirotaka Sakamoto, Chieko Aoyama, Hiromi Ando, Hiroyuki Sugimoto

    Scientific reports   10 ( 1 )   2845 - 2845   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    StarD7 is a phosphatidylcholine (PC)-specific lipid transfer protein essential for the maintenance of mitochondrial PC composition, morphogenesis, and respiration. Here, we studied the role of StarD7 in skeletal myoblast differentiation using mouse myoblast C2C12 cells and human primary myoblasts. Immunofluorescence and immuno-electron microscopy revealed that StarD7 was distributed in the cytosol, inner mitochondria space, and outer leaflet of the outer mitochondrial membrane in C2C12 cells. Unlike human kidney embryonic cell line HEK293 cells, the mitochondrial proteinase PARL was not involved in the processing and maturation of StarD7 in C2C12 cells. StarD7 was constantly expressed during myogenic differentiation of C2C12 cells. The siRNA-mediated knockdown of StarD7 in C2C12 cells and human primary myoblasts significantly impaired myogenic differentiation and reduced the expression of myomaker, myomerger and PGC-1α. The reduction in mitochondrial PC levels and oxygen consumption rates, decreased expression of myomaker, myomerger and PGC-1α, as well as impaired myogenic differentiation, were completely restored when the protein was reintroduced into StarD7-knockout C2C12 cells. These results suggest that StarD7 is important for skeletal myogenesis in mammals.

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  • Analyzing the effects of co-expression of chick (Gallus gallus) melanocortin receptors with either chick MRAP1 or MRAP2 in CHO cells on sensitivity to ACTH(1–24) or ACTH(1–13)NH2: Implications for the avian HPA axis and avian melanocortin circuits in the hypothalamus 査読

    Alexa L. Thomas, Fumihiko Maekawa, Takaharu Kawashima, Hirotaka Sakamoto, Tatsuya Sakamoto, Perry Davis, Robert M. Dores

    General and Comparative Endocrinology   256   50 - 56   2018年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Academic Press Inc.  

    In order to better understand the roles that melanocortin receptors (cMCRs) and melanocortin-2 receptor accessory proteins (cMRAP1 and cMRAP2) play in the HPA axis and hypothalamus, adrenal gland and hypothalamus mRNA from 1 day-old white leghorn chicks (Gallus gallus), were analyzed by real-time PCR. mRNA was also made for kidney, ovary, and liver. Mrap1 mRNA could be detected in adrenal tissue, but not in any of the other tissues, and mrap2 mRNA was also detected in the adrenal gland. Finally, all five melanocortin receptors mRNAs could be detected in the adrenal gland
    mc2r and mc5r mRNAs were the most abundant. To evaluate any potential interactions between MRAP1 and the MCRs that may occur in adrenal cells, individual chick mcr cDNA constructs were transiently expressed in CHO cells either in the presence or absence of a chick mrap1 cDNA, and the transfected cells were stimulated with hACTH(1–24) at concentrations ranging from 10−13 M to 10−6 M. As expected, MC2R required co-expression with MRAP1 for functional expression
    whereas, co-expression of cMC3R with cMRAP1 had no statistically significant effect on sensitivity to hACTH(1–24). However, co-expression of MC4R and MC5R with MRAP1, increased sensitivity for ACTH(1–24) by approximately 35 fold and 365 fold, respectively. However, co-expressing of cMRAP2 with these melanocortin receptors had no effect on sensitivity to hACTH(1–24). Since the real-time PCR analysis detected mrap2 mRNA and mc4r mRNA in the hypothalamus, the interaction between cMC4R and cMRAP2 with respect to sensitivity to ACTH(1–13)NH2 stimulation was also evaluated. However, no effect, either positive or negative, was observed. Finally, the highest levels of mc5r mRNA were detected in liver cells. This observation raises the possibility that in one-day old chicks, activation of the HPA axis may also involve a physiological response from liver cells.

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    その他リンク: http://orcid.org/0000-0002-6224-4591

  • The mineralo-corticoid receptor knockout in medaka is further validated by glucocorticoid receptor compensation 査読

    Tatsuya Sakamoto, Madoka Yoshiki, Hirotaka Sakamoto

    Scientific Data   4   924 - 928   2017年12月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    To study the critical role of mineralocorticoid signalling, we generated a constitutive mineralocorticoid receptor (MR)-knockout (KO) medaka as the first adult-viable MR-KO animal. This KO medaka displayed abnormal behaviours affected by visual stimuli. In contrast, the loss of MR did not result in overt phenotypic changes in osmoregulation, despite the well-known osmoregulatory functions of MR in mammals. Since glucocorticoid receptor (GR) has been suggested to compensate for loss of MR, we examined expression of duplicated GRs with markedly different ligand sensitivities, in various tissues. qRT-PCR results revealed that the absence of MR induced GR1 in the brain and eyes, but not in osmoregulatory organs. This reinforces the important functions of glucocorticoid signalling, but the minor role of mineralocorticoid signalling, in fish osmoregulation. Because both 11-deoxycorticosterone (DOC) and cortisol are ligands for MR, whereas GRs are specific to cortisol, GR1 signalling may compensate for the absence of cortisol-MR, rather than that of DOC-MR. Thus, this GR expression suggests that our MR-KO model can be used specifically to characterize DOC-MR signalling.

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    その他リンク: http://orcid.org/0000-0002-6224-4591

  • MORPHOLOGICAL AND MOLECULAR EVOLUTIONAL ANALYSES OF ITCH FOCUSED ON THE GASTRIN-RELEASING PEPTIDE SYSTEM IN MAMMALS 査読

    Keiko Takanami, Keita Satoh, Kazuyoshi Murata, Tatsuya Sakamoto, Hirotaka Sakamoto

    ACTA DERMATO-VENEREOLOGICA   97 ( 8 )   1049 - 1050   2017年9月

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    記述言語:英語   出版者・発行元:ACTA DERMATO-VENEREOLOGICA  

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  • Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish 査読

    Tatsuya Sakamoto, Madoka Yoshiki, Hideya Takahashi, Masayuki Yoshida, Yukiko Ogino, Toshitaka Ikeuchi, Tomoya Nakamachi, Norifumi Konno, Kouhei Matsuda, Hirotaka Sakamoto

    Scientific Reports   6   37991   2016年11月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    As in osmoregulation, mineralocorticoid signaling is implicated in the control of brain-behavior actions. Nevertheless, the understanding of this role is limited, partly due to the mortality of mineralocorticoid receptor (MR)-knockout (KO) mice due to impaired Na+ reabsorption. In teleost fish, a distinct mineralocorticoid system has only been identified recently. Here, we generated a constitutive MR-KO medaka as the first adult-viable MR-KO animal, since MR expression is modest in osmoregulatory organs but high in the brain of adult medaka as for most teleosts. Hyper-and hypo-osmoregulation were normal in MR-KO medaka. When we studied the behavioral phenotypes based on the central MR localization, however, MR-KO medaka failed to track moving dots despite having an increase in acceleration of swimming. These findings reinforce previous results showing a minor role for mineralocorticoid signaling in fish osmoregulation, and provide the first convincing evidence that MR is required for normal locomotor activity in response to visual motion stimuli, but not for the recognition of these stimuli per se. We suggest that MR potentially integrates brain-behavioral and visual responses, which might be a conserved function of mineralocorticoid signaling through vertebrates. Importantly, this fish model allows for the possible identification of novel aspects of mineralocorticoid signaling.

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  • Postnatal development of the gastrin-releasing peptide system in the lumbosacral spinal cord controlling male reproductive function in rats 査読

    Nao Katayama, Takumi Oti, Keiko Takanami, Tatsuya Sakamoto, Hirotaka Sakamoto*

    PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES   92 ( 2 )   69 - 75   2016年2月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN ACAD  

    A sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord, which projects to the lower spinal centers, controls erection and ejaculation in rats. However, little is known about the postnatal development of this system. In this study, we therefore examined the postnatal development of the male-dominant spinal GRP system and its sexual differentiation in rats using immunohistochemistry. Our results show that male-dominant expression of GRP is prominent from the onset of puberty and that sexually dimorphism persists into adulthood. These results suggest that androgen surge during male puberty plays an important role in the development and maintenance of the male-specific GRP function in the rat spinal cord.

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  • Comparative Anatomy of Gastrin-releasing Peptide Pathways in the Trigeminal Sensory System of Mouse and the Asian House Musk Shrew Suncus murinus 査読

    Keiko Takanami, Kaihei Inoue, Hiroki Mukai, Kei Tamura, Takamichi Jogahara, Sen-ichi Oda, Mitsuhiro Kawata, Tatsuya Sakamoto, Hirotaka Sakamoto*

    ACTA HISTOCHEMICA ET CYTOCHEMICA   49 ( 6 )   181 - 190   2016年

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPAN SOC HISTOCHEMISTRY & CYTOCHEMISTRY  

    Gastrin-releasing peptide (GRP) has recently been identified as an itch-signaling molecule in the primary afferents and spinal cord of rodents. However, little information exists on the expression and localization of GRP in the trigeminal somatosensory system other than in rats. We examined the generality of the trigeminal GRP system in mammals using two distinct species, suncus as a model of specialized placental mammals known to have a well-developed trigeminal sensory system and mice as a representative small laboratory animal. We first analyzed the gross morphology of the trigeminal somatosensory system in suncus to provide a brainstem atlas on which to map GRP distribution. Immunohistochemical analyses showed that 8% of trigeminal ganglion neurons in suncus and 6% in mice expressed GRP. Expression was restricted to cells with smaller somata. The GRP-containing fibers were densely distributed in the superficial layers of the caudal part of the trigeminal spinal nucleus (Vc) but rare in the rostral parts, both in suncus and mice. Expression of GRP receptor mRNA and protein was also detected in the Vc of suncus. Taken together, these results suggest that the trigeminal GRP system mediating itch sensation is conserved in mammals.

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  • Three-dimensional visualization of multiple synapses in thick sections using high-voltage electron microscopy in the rat spinal cord 査読

    Keita Satoh, Keiko Takanami, Kazuyoshi Murata, Mitsuhiro Kawata, Tatsuya Sakamoto, Hirotaka Sakamoto*

    Data in Brief   4   566 - 570   2015年9月

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    担当区分:最終著者, 責任著者   記述言語:英語  

    DOI: 10.1016/j.dib.2015.07.005

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  • Oxytocin and the gastrin-releasing peptide system in the spinal cord: Implications for male sexual problems 査読

    Sakamoto H*, Oti T

    Interdisciplinary Information Sciences   21   235 - 242   2015年9月

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    担当区分:筆頭著者, 責任著者   記述言語:英語  

    DOI: 10.4036/iis.2015.B.08

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  • Osmotic/ionic status of body fluids in the euryhaline cephalopod suggest possible parallel evolution of osmoregulation 査読

    Tatsuya Sakamoto, Satoshi Ogawa, Yudai Nishiyama, Chiaki Akada, Hideya Takahashi, Taro Watanabe, Hiroyuki Minakata, Hirotaka Sakamoto

    SCIENTIFIC REPORTS   5   14469   2015年9月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Acclimation from marine to dilute environments constitutes among the dramatic evolutionary transitions in the history of life. Such adaptations have evolved in multiple lineages, but studies of the blood/hemolymph homeostasis mechanisms are limited to those using evolutionarily advanced Deuterostome (chordates) and Ecdysozoa (crustaceans). Here, we examined hemolymph homeostasis in the advanced Lophotrochozoa/mollusc, the other unexplored taxa, and its possible regulation by the vasopressin/oxytocin superfamily peptides known to be implicated in fluid homeostasis in Chordata and Arthropoda. The hemolymph osmotic and ionic status in the euryhaline cephalopod (Octopus ocellatus) following transfer from 30-ppt normal seawater to 20 ppt salinity indicate hyperosmo- and hyperionoregulatory abilities for more than 1 week, as in crustaceans and teleost fish. While ventilation frequency decreased by 1 day, Na+/K+-ATPase activity, which has been generally implicated in ion transport, was induced in two of the eight posterior gills after 1 week. In addition, the octopuses were intravenously injected with 1 or 100 ng/g octopressin or cephalotocin, which are Octopus vasopressin/oxytocin orthologs. After 1 day, octopressin, but not cephalotocin, decreased the hemolymph osmolality and Ca concentrations, as well as urinary Na concentrations. These data provide evidence for possible parallel evolution in hyperionoregulatory mechanisms and coordination by conserved peptides.

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  • Neurohypophysial Hormones Regulate Amphibious Behaviour in the Mudskipper Goby 査読

    Tatsuya Sakamoto, Yudai Nishiyama, Aoi Ikeda, Hideya Takahashi, Susumu Hyodo, Nao Kagawa, Hirotaka Sakamoto

    PLOS ONE   10 ( 7 )   e0134605   2015年7月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PUBLIC LIBRARY SCIENCE  

    The neurohypophysial hormones, arginine vasotocin and isotocin, regulate both hydromineral balance and social behaviors in fish. In the amphibious mudskipper, Periophthalmus modestus, we previously found arginine-vasotocin-specific regulation of aggressive behavior, including migration of the submissive subordinate into water. This migration also implies the need for adaptation to dehydration. Here, we examined the effects of arginine vasotocin and isotocin administration on the amphibious behavior of individual mudskippers in vivo. The mudskippers remained in the water for an increased period of time after 1-8 h of intracerebroventricular (ICV) injection with 500 pg/g arginine vasotocin or isotocin. The 'frequency of migration' was decreased after ICV injection of arginine vasotocin or isotocin, reflecting a tendency to remain in the water. ICV injections of isotocin receptor antagonist with arginine vasotocin or isotocin inhibited all of these hormonal effects. In animals kept out of water, mRNA expression of brain arginine vasotocin and isotocin precursors increased 3- and 1.5-fold, respectively. Given the relatively wide distribution of arginine vasotocin fibres throughout the mudskipper brain, induction of arginine vasotocin and isotocin under terrestrial conditions may be involved also in the preference for an aquatic habitat as ligands for brain isotocin receptors.

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  • Effective synaptome analysis of itch-mediating neurons in the spinal cord: A novel immunohistochemical methodology using high-voltage electron microscopy 査読

    Keita Satoh, Keiko Takanami, Kazuyoshi Murata, Mitsuhiro Kawata, Tatsuya Sakamoto, Hirotaka Sakamoto

    NEUROSCIENCE LETTERS   599   86 - 91   2015年7月

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.neulet.2015.05.031

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  • Quality Control of Photosystem II: Direct Imaging of the Changes in the Thylakoid Structure and Distribution of FtsH Proteases in Spinach Chloroplasts under Light Stress 査読

    Miho Yoshioka-Nishimura, Daisuke Nanba, Takashi Takaki, Chikako Ohba, Nodoka Tsumura, Noriko Morita, Hirotaka Sakamoto, Kazuyoshi Murata, Yasusi Yamamoto

    PLANT AND CELL PHYSIOLOGY   55 ( 7 )   1255 - 1265   2014年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:OXFORD UNIV PRESS  

    Under light stress, the reaction center-binding protein D1 of PSII is photo-oxidatively damaged and removed from PSII complexes by proteases located in the chloroplast. A protease considered to be responsible for degradation of the damaged D1 protein is the metalloprotease FtsH. We showed previously that the active hexameric FtsH protease is abundant at the grana margin and the grana end membranes, and this homo-complex removes the photodamaged D1 protein in the grana. Here, we showed a change in the distribution of FtsH in spinach thylakoids during excessive illumination by transmission electron microscopy (TEM) and immunogold labeling of FtsH. The change in distribution of the protease was accompanied by structural changes to the thylakoids, which we detected using spinach leaves by TEM after chemical fixation of the samples. Quantitative analyses showed several characteristic changes in the structure of the thylakoids, including shrinkage of the grana, outward bending of the marginal portions of the thylakoids and an increase in the height of the grana stacks under excessive illumination. The increase in the height of the grana stacks may include swelling of the thylakoids and an increase in the partition gaps between the thylakoids. These data strongly suggest that excessive illumination induces partial unstacking of the thylakoids, which enables FtsH to access easily the photodamaged D1 protein. Finally three-dimensional tomography of the grana was recorded to observe the effect of light stress on the overall structure of the thylakoids.

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  • Distribution of Gastrin-Releasing Peptide in the Rat Trigeminal and Spinal Somatosensory Systems 査読

    Keiko Takanami, Hirotaka Sakamoto, Ken Ichi Matsuda, Keita Satoh, Takashi Tanida, Shunji Yamada, Kaihei Inoue, Takumi Oti, Tatsuya Sakamoto, Mitsuhiro Kawata

    JOURNAL OF COMPARATIVE NEUROLOGY   522 ( 8 )   1858 - 1873   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-BLACKWELL  

    Gastrin-releasing peptide (GRP) has recently been identified as an itch-specific neuropeptide in the spinal sensory system in mice, but there are no reports of the expression and distribution of GRP in the trigeminal sensory system in mammals. We characterized and compared GRP-immunoreactive (ir) neurons in the trigeminal ganglion (TG) with those in the rat spinal dorsal root ganglion (DRG). GRP immunoreactivity was expressed in 12% of TG and 6% of DRG neurons and was restricted to the small- and medium-sized type cells. In both the TG and DRG, many GRP-ir neurons also expressed substance P and calcitonin gene-related peptide, but not isolectin B-4. The different proportions of GRP and transient receptor potential vanilloid 1 double-positive neurons in the TG and DRG imply that itch sensations via the TG and DRG pathways are transmitted through distinct mechanisms. The distribution of the axon terminals of GRP-ir primary afferents and their synaptic connectivity with the rat trigeminal sensory nuclei and spinal dorsal horn were investigated by using light and electron microscopic histochemistry. Although GRP-ir fibers were rarely observed in the trigeminal sensory nucleus principalis, oralis, and interpolaris, they were predominant in the superficial layers of the trigeminal sensory nucleus caudalis (Vc), similar to the spinal dorsal horn. Ultrastructural analysis revealed that GRP-ir terminals contained clear microvesicles and large dense-cored vesicles, and formed asymmetric synaptic contacts with a few dendrites in the Vc and spinal dorsal horn. These results suggest that GRP-dependent orofacial and spinal pruriceptive inputs are processed mainly in the superficial laminae of the Vc and spinal dorsal horn. J. Comp. Neurol. 522:1858-1873, 2014. (c) 2013 Wiley Periodicals, Inc.

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  • Identification of CNS Neurons Innervating the Levator Ani and Ventral Bulbospongiosus Muscles in Male Rats 査読

    Amy D. Dobberfuhl, Takumi Oti, Hirotaka Sakamoto, Lesley Marson

    JOURNAL OF SEXUAL MEDICINE   11 ( 3 )   664 - 677   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY  

    IntroductionThe pelvic striated muscles play an important role in mediating erections and ejaculation, and together these muscles compose a tightly coordinated neuromuscular system that is androgen sensitive and sexually dimorphic.
    AimTo identify spinal and brains neurons involved in the control of the levator ani (LA) and bulbospongiosus (BS) in the male adult and preadolescent rat.
    MethodsRats were anesthetized, and the transsynaptic retrograde tracer pseudorabies virus (PRV) was injected into the LA muscle of adults or the ventral BS muscle in 30-day-old rats. After 3-5 days rats were sacrificed, and PRV-labeled neurons in the spinal cords and brains were identified using immunohistochemistry. The presence of gastrin-releasing peptide (GRP) in the lumbar spinal neurons was examined.
    Main Outcomes MeasuresThe location and number of PRV-labeled neurons in the spinal cord and brain and GRP colocalization in the lumbar spinal cord.
    ResultsPRV-labeled spinal interneurons were found distributed throughout T11-S1 of the spinal cord, subsequent to dorsal medial motoneuron infection. The majority of spinal interneurons were found in the lumbosacral spinal cord in the region of the dorsal gray commissure and parasympathetic preganglionic neurons. Preadolescent rats had more PRV-labeled spinal interneurons at L5-S1 where the motoneurons were located but relatively less spread rostrally in the spinal cord compared with adults. Lumbar spinothalmic neurons in medial gray of L3-L4 co-localized PRV and GRP. In the brain consistent labeling was seen in areas known to be involved in male sexual behavior including the ventrolateral medulla, hypothalamic paraventricular nucleus, and medial preoptic area.
    ConclusionCommon spinal and brain pathways project to the LA and BS muscles in the rat suggesting that these muscles act together to coordinate male sexual reflexes. Differences may exist in the amount of synaptic connections/neuronal pathways in adolescents compared with adults. Dobberfuhl AD, Oti T, Sakamoto H, and Marson L. Identification of CNS neurons innervating the levator ani and ventral bulbospongiosus muscles in male rats. J Sex Med 2014;11:664-677.

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  • Androgen regulates development of the sexually dimorphic gastrin-releasing peptide neuron system in the lumbar spinal cord: Evidence from a mouse line lacking androgen receptor in the nervous system 査読

    Hirotaka Sakamoto, Kazuhiro Saito, Clarisse Marie-Luce, Kalina Raskin, Takumi Oti, Keita Satoh, Kei Tamura, Tatsuya Sakamoto, Sakina Mhaouty-Kodja

    NEUROSCIENCE LETTERS   558   109 - 114   2014年1月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • The gastrin-releasing peptide receptor (GRPR) in the spinal cord as a novel pharmacological target 査読

    Keiko Takanami, Hirotaka Sakamoto

    CURRENT NEUROPHARMACOLOGY   12 ( 5 )   434 - 443   2014年

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    担当区分:最終著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BENTHAM SCIENCE PUBL LTD  

    Gastrin-releasing peptide (GRP) is a mammalian neuropeptide that acts through the G protein-coupled receptor, GRP receptor (GRPR). Increasing evidence indicates that GRPR-mediated signaling in the central nervous system plays an important role in many physiological processes in mammals. Additionally, we have recently reported that the GRP system within the lumbosacral spinal cord not only controls erection but also triggers ejaculation in male rats. This system of GRP neurons is sexually dimorphic, being prominent in male rats but vestigial or absent in females. It is suggested that the sexually dimorphic GRP/GRPR system in the lumbosacral spinal cord plays a critical role in the regulation of male sexual function. In parallel, it has been reported that the somatosensory GRP/GRPR system in the spinal cord contributes to the regulation of itch specific transmission independently of the pain transmission. Interestingly, these two distinct functions in the same spinal region are both regulated by the neuropeptide, GRP. In this report, we review findings on recently identified GRP/GRPR systems in the spinal cord. These GRP/GRPR systems in the spinal cord provide new insights into pharmacological treatments for psychogenic erectile dysfunction as well as for chronic pruritus.

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  • Sexually dimorphic nuclei in the spinal cord control male sexual functions 査読

    H. Sakamoto

    Frontiers in Neuroscience   8 ( 8 )   184   2014年

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:英語  

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  • Potential roles of arginine-vasotocin in the regulation of aggressive behavior in the mudskipper (Periophthalmus modestus) 査読

    Nao Kagawa, Yudai Nishiyama, Kanoko Kato, Hideya Takahashi, Yasuhisa Kobayashi, Hirotaka Sakamoto, Tatsuya Sakamoto

    General and Comparative Endocrinology   194   257 - 263   2013年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Academic Press Inc.  

    The hypothalamic hormones, arginine-vasotocin (VT) and isotocin (IT), play central roles in osmoregulation and in the regulation of social behaviors including aggressive behavior in many vertebrates including fish. Here, we examined whether these hormones are associated with aggressive behavior in the mudskipper (Periophthalmus modestus). The mudskipper is an amphibious fish, which lives in the brackish water of river mouths and displays unique aggressive behavior. Upon introduction to each other in an experimental tank with aquatic and terrestrial areas, a pair of males can be classified as aggressive dominant or submissive subordinate based on the frequency of their aggressive acts, which is significantly higher in dominant male. Additionally, the length of stay in terrestrial area of dominant was longer than that of the subordinate. The latter remained in aquatic area almost throughout the period of behavioral observation. The expression of brain VT mRNA was significantly higher in subordinate than in dominant, whereas neither IT mRNA expression nor plasma cortisol level differed between subordinate and dominant male. On the other hand, an intracerebroventricular injection of VT increased aggressive behaviors in mudskippers. In addition to known roles of VT in mediation of aggressive behavior, these results may shed light on the role of endogenous VT toward water migration in submissive mudskippers. The amphibious fish is a valuable experimental model to observe the relationship between effects of central VT on the osmoregulation and social behavioral regulation in vertebrates. © 2013.

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  • Ultrahigh voltage electron microscopy links neuroanatomy and neuroscience/neuroendocrinology. 査読

    Sakamoto H*, Kawata M

    Anatomy Research International   2012   948704   2012年5月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • Brain-spinal cord neural circuits controlling male sexual function and behavior 査読

    Hirotaka Sakamoto

    NEUROSCIENCE RESEARCH   72 ( 2 )   103 - 116   2012年2月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Men and women exhibit differences in sexual behavior. This indicates that neural circuits within the central nervous system (CNS) that control sexual behavior differ between the sexes, although differences in behavior are also influenced by sociocultural and hormonal factors. Sexual differentiation of the body and brain occurs during the embryonic and neonatal periods in humans and persists into adulthood with relatively low plasticity. Male sexual behavior is complex and depends on intrinsic and extrinsic factors, including olfactory, somatosensory and visceral cues. Many advances in our understanding of sexually dimorphic neural circuits have been achieved in animal models, but major issues are yet to be resolved. This review summarizes the sexually dimorphic nuclei controlling male sexual function in the rodent CNS and focuses on the interactions of the brain-spinal cord neural networks controlling male sexual behavior. Possible factors that relate findings from animal studies to human behavior are also discussed. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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  • Rapid signaling of steroid hormones in the vertebrate nervous system 査読

    Hirotaka Sakamoto, Hideya Takahashi, Ken-Ichi Matsuda, Mayumi Nishi, Keiko Takanami, Maho Ogoshi, Tatsuya Sakamoto, Mitsuhiro Kawata

    FRONTIERS IN BIOSCIENCE-LANDMARK   17   996 - 1019   2012年1月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:FRONTIERS IN BIOSCIENCE INC  

    Steroid hormones easily cross the blood-brain barrier because of their physicochemical lipid solubility. The hormones act through nuclear receptor-mediated mechanisms and modulate gene transcription. In contrast to their genomic actions, the non-genomic rapid action of steroid hormones, acting via various types of membrane-associated receptors, reveals pharmacological properties that are distinct from the actions of the intracellular nuclear receptors. As a result, non-genomic rapid actions have gained increased scientific interest. However, insight into the phylogenic and/or comparative actions of steroids in the brain is still poorly understood. In this review, we summarize recent findings concerning the rapid, non-genomic signaling of steroid hormones in the vertebrate central nervous system, and we discuss (using a comparative view from fish to mammals) recently published data regarding the mechanism underlying physiology and behavior.

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  • Immunohistochemical Analysis of the Effects of Estrogen on Intraarticular Neurogenic Inflammation in a Rat Anterior Cruciate Ligament Transection Model of Osteoarthritis 査読

    Atsuhiko Yoshida, Toru Morihara, Ken-ichi Matsuda, Hirotaka Sakamoto, Yuji Arai, Yoshikazu Kida, Mitsuhiro Kawata, Toshikazu Kubo

    CONNECTIVE TISSUE RESEARCH   53 ( 3 )   197 - 206   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INFORMA HEALTHCARE  

    Synovitis is considered as one of the factors associated with the pathogenesis of osteoarthritis (OA). There is currently a significant amount of research linking estrogen deficiencies with the development of OA in estrogen-deficient women, including postmenopausal women; however, the exact etiology remains unclear. Various neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been shown to contribute to synovitis in OA joints, and the influence of estrogen on the expressions of SP and CGRP in the synovium of OA joints has been noted. After ovariectomy (OVX) followed by estradiol (E2) replacement, 24 female rats were divided into three groups: OVX group, OVX + E2 replacement group (E2 group), and a sham group. All rats underwent transection of the anterior cruciate ligament at the same time. After 30 days, the histological findings of knee joints by hematoxylin-eosin staining and immunofluorescence staining of protein gene product 9.5 (pan-neuronal marker), SP, and CGRP were compared among experimental groups. The degree of synovitis in the OVX group was higher than in the E2 and sham groups. No significant differences in the density of protein gene product 9.5-immunoreactive nerve fibers were observed among the three experimental groups, but the density of SP- or CGRP-immunoreactive nerve fibers in the OVX group was significantly higher than in the E2 and sham groups. These findings suggest that estrogen partly regulates intraarticular neurogenic inflammation in OA joints by modulating the expressions of neuropeptides in the synovium.

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  • Corticosteroids stimulate the amphibious behavior in mudskipper: Potential role of mineralocorticoid receptors in teleost fish 査読

    Tatsuya Sakamoto, Chie Mori, Shogo Minami, Hideya Takahashi, Tsukasa Abe, Daisuke Ojima, Maho Ogoshi, Hirotaka Sakamoto

    PHYSIOLOGY & BEHAVIOR   104 ( 5 )   923 - 928   2011年10月

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    担当区分:最終著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    It has long been held that cortisol, a glucocorticoid in many vertebrates, carries out both glucocorticoid and mineralocorticoid actions in teleost fish. However, 11-deoxycorticosterone (DOC) has been identified as a specific endogenous ligand for the teleostean mineralocorticoid receptor (MR). Furthermore, the expressions of MR mRNA are modest in the osmoregulatory organs, but considerably higher in the brain of most teleosts. These recent findings suggest that the mineralocorticoid system (DOC/MR) may carry out some behavioral functions in fish. To test this possibility, we examined the effects of cortisol and DOC administration in the amphibious behavior in mudskipper (Periophthalmus modestus) in vivo. It was found that mudskippers remained in the water for an increased period of time when they were immersed into 5 mu M DOC or cortisol for 8 h. Additionally, an exposure to 25 mu M DOC for 4 to 8 h caused a decreased migratory frequency of mudskippers to the water, reflected a tendency to remain in the water. It was further observed that after 8 h of intracerebroventricular (ICV) injection with 0.3 pmol DOC or cortisol the staying period in the water increased in fish. The migratory frequency was decreased after ICV DOC injection which indicated that fishes stayed in the water. Concurrent ICV injections of cortisol with RU486 [a specific glucocorticoid-receptor (GR) antagonist] inhibited only the partial effects of cortisol. Together with no changes in the plasma DOC concentrations under terrestrial conditions, these results indicate the involvement of brain MRs as cortisol receptors in the preference for an aquatic habitat of mudskippers. Although the role of GR signaling cannot be excluded in the aquatic preference, our data further suggest that the MR may play an important role in the brain dependent behaviors of teleost fish. (C) 2011 Elsevier Inc. All rights reserved.

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  • The gastrin-releasing peptide system in the spinal cord mediates masculine sexual function 査読

    Hirotaka Sakamoto*

    ANATOMICAL SCIENCE INTERNATIONAL   86 ( 1 )   19 - 29   2011年3月

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:英語   出版者・発行元:SPRINGER  

    The lumbar spinal segments are of particular interest because they are sexually dimorphic and contain several neuronal circuits that are important in eliciting male sexual responses such as erection and ejaculation. Gastrin-releasing peptide (GRP) is a member of the bombesin-like peptide family first isolated from the porcine stomach. A collection of neurons in the lumbar spinal cord (L3-L4 level) of male rats projects to the lower lumbar spinal cord (L5-L6 level), releasing GRP onto somatic and autonomic centers known to regulate male sexual reflexes. All these target neurons express and localize specific receptors for GRP. This system of GRP neurons is sexually dimorphic, being prominent in male rats but vestigial in females. The system is completely feminine in genetically XY rats with a dysfunctional androgen receptor gene, demonstrating the androgen-dependent nature of the dimorphism. Pharmacological stimulation of GRP receptors in this spinal region remarkably restores sexual reflexes in castrated male rats. Exposure of male rats to a severe traumatic stress decreases the local content and the axonal distribution of GRP in the lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Administration of a specific agonist for GRP receptors restores penile reflexes in the traumatic stress-exposed male rats. This review summarizes findings on this recently identified spinal GRP system, which may be vulnerable to stress, that controls male reproductive function. The identification of a male-specific neuronal system regulating sexual functions offers new avenues for potential therapeutic approaches to masculine reproductive dysfunction.

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  • Biosynthesis, mode of action, and functional significance of neurosteroids in the purkinje cell 査読

    Kazuyoshi Tsutsui, Kazuyoshi Ukena, Hirotaka Sakamoto, Shin-Ichiro Okuyama, Shogo Haraguchi

    Frontiers in Endocrinology   2   61   2011年

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    記述言語:英語  

    The brain has traditionally been considered to be a target site of peripheral steroid hormones. In addition to this classical concept, we now know that the brain has the capacity to synthesize steroids de novo from cholesterol, the so-called "neurosteroids." In the middle 1990s, the Purkinje cell, an important cerebellar neuron, was identified as a major site for neurosteroid formation in the brain of mammals and other vertebrates. This discovery has provided the opportunity to understand neuronal neurosteroidogenesis in the brain. In addition, biological actions of neurosteroids are becoming clear by the studies using the Purkinje cell, an excellent cellular model, which is known to play an important role in memory and learning processes. Based on the studies on mammals over the past decade, it is considered that the Purkinje cell actively synthesizes progesterone and estradiol from cholesterol during neonatal life, when cerebellar neuronal circuit formation occurs. Both progesterone and estradiol promote dendritic growth, spinogenesis, and synaptogenesis via each cognate nuclear receptor in the developing Purkinje cell. Such neurosteroid actions mediated by neurotrophic factors may contribute to the formation of cerebellar neuronal circuit during neonatal life. 3α,5α-Tetrahydroprogesterone (allopregnanolone), a progesterone metabolite, is also synthesized in the cerebellum and considered to act as a survival factor of Purkinje cells in the neonate. This review summarizes the current knowledge regarding the biosynthesis, mode of action, and functional significance of neurosteroids in the Purkinje cell during development in terms of synaptic formation of cerebellar neuronal networks. © 2011 Tsutsui, Ukena, Sakamoto, Okuyama and Haraguchi.

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  • The neurobiology of psychogenic erectile dysfunction in the spinal cord 査読

    Hirotaka Sakamoto*

    JOURNAL OF ANDROLOGY   31 ( 6 )   519 - 526   2010年11月

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    担当区分:筆頭著者, 最終著者, 責任著者   記述言語:英語   出版者・発行元:AMER SOC ANDROLOGY, INC  

    We recently reported a previously unknown peptider gic system within the lumbosacral spinal cord that uses gastrin releasing peptide (GRP) to trigger erection and ejaculation in male rats Many men suffering from stress including posttraumatic stress disorder (PTSD) and major depressive disorder report sexual dysfunction Sexual dysfunction in men suffering from stress and major depressive disorder is traditionally treated via psychological counseling To determine whether acute severe stress could alter the male specific GRP system, we used single prolonged stress (SPS) exposure in a putative rat model for PTSD Exposure of male rats to SPS decreases the local content and the axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo Pharmacological stimulation of GRP receptors remarkably restores penile reflexes in SPS exposed male rats and in castrated male rats The administration of a GRP agonist to these animal models interestingly induces spontaneous ejaculation in a dose dependent manner Furthermore although the circulating level of androgens is normal 1 week after SPS exposure there is a significant decrease in the expression of androgen receptor protein in lumbar segments 3 and 4 of the spinal cord This might make the spinal center less responsive to androgens In this report I review findings on a recently identified spinal GRP system that could be vulnerable to stress and that controls male reproductive function This system provides new insights into the clinical treatment of psychogenic erectile dysfunction triggered by stress and psychiatric disorders

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  • Induction of the arginine vasopressin-enhanced green fluorescent protein fusion transgene in the rat locus coeruleus 査読

    Miwako Todoroki, Yoichi Ueta, Hiroaki Fujihara, Hiroki Otsubo, Minori Shibata, Hirofumi Hashimoto, Mizuki Kobayashi, Hirotaka Sakamoto, Mitsuhiro Kawata, Govindan Dayanithi, David Murphy, Hisanori Hiro, Ken Takahashi, Shoji Nagata

    STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS   13 ( 4 )   281 - 292   2010年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:INFORMA HEALTHCARE  

    We examined the effects of intracerebroventricular (i.c.v.) administration of colchicine on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) fusion gene in rats. In rats administered i.c.v. vehicle ( control), eGFP fluorescence was observed in the supraoptic nucleus ( SON), the magnocellular division of the paraventricular nucleus (PVN), the suprachiasmatic nucleus (SCN), the median eminence ( ME) and the posterior pituitary. Two days after i.c.v. administration of colchicine, eGFP fluorescence was markedly increased in the SON, the magnocellular and parvocellular divisions of the PVN, the SCN, the ME and the locus coeruleus (LC). Immunohistochemical staining for eGFP confirmed the distribution of fluorescence in both groups. In the colchicines-administered groups, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localised with TH-immunoreactivity in the LC. Similarly, in situ hybridization histochemistry for eGFP mRNA revealed a significant increase in gene expression in the LC, the SON and the PVN 12-48 h after administration of colchicine. Our results indicate that the synthesis of AVP-eGFP is upregulated in noradrenergic neurones in the LC after colchicine administration. This implies that AVP and noradrenaline, originating from LC neurones, might play a role in response to chronic stress.

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  • Aldosterone-Sensitive Nucleus Tractus Solitarius Neurons Regulate Sensitivity of the Baroreceptor Reflex in High Sodium-Loaded Rats 査読

    Tomoharu Masuda, Yasutoshi Hirabara, Yusuke Nakamura, Akiko Chishaki, Mai Tsuruhisa, Masayuki Miyakawa, Kenji Honda, Ryo Saito, Hirotaka Sakamoto, Mitsuhiro Kawata, Yukio Takano

    JOURNAL OF PHARMACOLOGICAL SCIENCES   112 ( 4 )   482 - 486   2010年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

    We examined the role of aldosterone-sensitive neurons in the nucleus tractus solitarius (NTS) in the arterial baroreceptor reflex (baroreflex) function. Baroreflex sensitivity was induced by phenylephrine in high sodium-loaded rats and was significantly reduced. This baroreflex sensitivity was reversed by microinjection of the mineralocorticoid receptor (MR) antagonist eplerenone into the NTS. 11 beta-Hydroxysteroid dehydrogenase type 2 neurons and MR were also identified in the NTS. These data suggest that the aldosterone-sensitive neurons in the NTS may have an important role in baroreflex function.

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  • High-Voltage Electron Microscopy Reveals Direct Synaptic Inputs from a Spinal Gastrin-Releasing Peptide System to Neurons of the Spinal Nucleus of Bulbocavernosus 査読

    Hirotaka Sakamoto*, Tatsuo Arii, Mitsuhiro Kawata

    ENDOCRINOLOGY   151 ( 1 )   417 - 421   2010年1月

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    担当区分:筆頭著者, 責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ENDOCRINE SOC  

    The spinal nucleus of bulbocavernosus (SNB) is a sexually dimorphic motor nucleus located in the anterior horn of the fifth and sixth lumbar segments of the spinal cord that plays a significant role in male sexual function. We recently found that a sexually dimorphic expression of gastrin-releasing peptide (GRP) in the lumbar spinal cord regulates male copulatory reflexes. Although it is reported that these systems are both profoundly regulated by circulating androgen levels in male rats, no direct evidence has been reported regarding GRP synaptic inputs onto SNB motoneurons. The aim of the current study was to determine the axodendritic synaptic inputs of spinal GRP neurons to SNB motoneurons. Immunoelectron microscopy, combined with a retrograde tracing technique using high-voltage electron microscopy (HVEM), provided a three-dimensional visualization of synaptic contacts from the GRP system in the lumbar spinal cord onto SNB motoneurons. HVEM analysis clearly demonstrated that GRP-immunoreactive axon terminals directly contact dendrites that extend into the dorsal gray commissure from the SNB. These HVEM findings provide an ultrastructural basis for understanding how the spinal GRP system regulates male sexual behavior. (Endocrinology 151: 417-421, 2010)

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  • Expression of G protein-coupled receptor 30 in the spinal somatosensory system 査読

    Keiko Takanami, Hirotaka Sakamoto, Ken-Ichi Matsuda, Koji Hosokawa, Mayumi Nishi, Eric R. Prossnitz, Mitsuhiro Kawata

    BRAIN RESEARCH   1310   17 - 28   2010年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCIENCE BV  

    Estrogens were originally identified as the primary sex steroid hormones in females and regulators of reproductive function and sexual behavior, but it has long been suggested that estrogens also have local effects on the somatosensory system at the spinal cord level. it is well known that the effects of estrogens are mediated by nuclear estrogen receptors (ERs) through genomic action, but recently a membrane-bound G protein-coupled receptor, GPR30, was identified as a non-genomic estrogen receptor. in this study we investigated the presence and localization of GPR30 in the rat spinal cord and dorsal root ganglion (DRG) in comparison with ER alpha. Using immunohistochemistry and in situ hybridization, we showed the expression of GPR30 in DRG neurons in male and female rats at mRNA and protein levels without specific sexual difference. A dense accumulation of GPR30 immunoreactivity was observed in the outer layer of the spinal dorsal horn, and selective spinal dorsal rhizotomy revealed that GPR30 was transported from the DRG to terminals located in the spinal dorsal horn. GPR30 expression was downregulated in DRG neurons of ovariectomized female rats. The spinal somatosensory system might be modulated by estradiol via putative membrane ER, GPR30-mediated mechanism. (C) 2009 Elsevier B.V. All rights reserved.

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  • Characterization of In Vivo Effects of Platelet-Rich Plasma and Biodegradable Gelatin Hydrogel Microspheres on Degenerated Intervertebral Discs 査読

    Kazuhide Sawamura, Takumi Ikeda, Masateru Nagae, Shin-ichi Okamoto, Yasuo Mikami, Hitoshi Hase, Kazuya Ikoma, Tetsuya Yamada, Hirotaka Sakamoto, Ken-ichi Matsuda, Yasuhiko Tabata, Mitsuhiro Kawata, Toshikazu Kubo

    TISSUE ENGINEERING PART A   15 ( 12 )   3719 - 3727   2009年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT, INC  

    We have previously shown that administration of platelet-rich plasma-impregnated gelatin hydrogel microspheres (PRP-GHMs) into a degenerated intervertebral disc (IVD) markedly suppresses progression of IVD degeneration. In the current study, we characterized the in vivo effects of PRP-GHM treatment in a degenerated IVD model in rabbit. On magnetic resonance images, the IVD height was significantly greater after treatment with PRP-GHMs compared with phosphate-buffered saline-impregnated GHMs, PRP without GHMs, and needle puncture only. Water content was also preserved in PRP-GHM-treated IVDs. Consistent with this observation, the mRNA expression of proteoglycan core protein and type II collagen was significantly higher after PRP-GHM treatment compared with other treatment groups. No proliferating cells were found in the nucleus pulposus and inner annulus fibrosus in any groups, but the number of apoptotic cells in the nucleus pulposus after PRP-GHM treatment was significantly lower than that after other treatments. These results provide an improved understanding of the therapeutic effects of PRP-GHM treatment of degenerated IVDs.

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  • In Vivo Effects of Ovarian Steroid Hormones on the Expressions of Estrogen Receptors and the Composition of Extracellular Matrix in the Anterior Cruciate Ligament in Rats 査読

    Atsuhiko Yoshida, Toru Morihara, Yoshiteru Kajikawa, Yuji Arai, Yasushi Oshima, Toshikazu Kubo, Ken-ichi Matsuda, Hirotaka Sakamoto, Mitsuhiro Kawata

    CONNECTIVE TISSUE RESEARCH   50 ( 2 )   121 - 131   2009年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Female athletes have a significantly higher rate of anterior cruciate ligament (ACL) injury than their male counterparts. Sex steroid hormones are considered to have an influence as risk factors for female ACL injuries. We hypothesized that estrogen and progesterone have specific and synergistic influences on the composition of extracellular matrix in ACL. By ovariectomy (OVX) followed by subcutaneous estradiol (E2) and/or progesterone (P4) replacement, 40 female rats were divided into 5 groups: E2, P4, combined E2 and P4 (EP), OVX control, and sham group. After 30 days, using undecalcified sections of knee joints in conjunction with immunofluorescence staining of estrogen receptor and (ER and ER), collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP), the immunoreactivities of these proteins in two distinct parts of ACL, proximal and middle portions, were compared semiquantitatively among experimental groups. By E2 replacement, the expressions of ER in ACL fibroblasts were elevated compared to the OVX group. At the proximal portion, the immunoreactivities of type 1 collagen by E2 replacement, type 3 collagen by P4 replacement, and COMP by E2 or P4 replacement were significantly reduced. At the middle portion, the immunoreactivity of type 3 collagen was significantly elevated by E2 replacement. However, no differences were observed between the sham and OVX groups. These findings suggest that ACL is ER-dependent and that ovarian hormones alter ligament tissue composition, especially at the proximal portion. Female hormonal influences are partly involved in the biological properties of ACL.

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  • Androgen action in the brain and spinal cord for the regulation of male sexual behaviors 査読

    Ken-ichi Matsuda, Hirotaka Sakamoto, Mitsuhiro Kawata

    CURRENT OPINION IN PHARMACOLOGY   8 ( 6 )   747 - 751   2008年12月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI LTD  

    Circulating levels of androgens determine the sexual differentiation of the brain and spinal cord at a critical period, Although estradiol, which is converted from testosterone by aromatase action, can explain the cytological basis for the sexual dimorphism, androgen has its own regulatory mechanism to promote male-specific behavior through receptors. The central nervous system (CNS) employs a sex-specific neuronal network involving peptides and steroids for the expression of the sexual phenotype. Elucidation of the molecular mechanism along with the neuroanatomical background should guide the development of novel pharmacotherapeutics for sexual behavior dysfunction.

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  • Expression and intracellular distribution of the G protein-coupled receptor 30 in rat hippocampal formation 査読

    KenIchi Matsuda, Hirotaka Sakamoto, Hiroko Mori, Koji Hosokawa, Akeo Kawamura, Minoru Itose, Mayumi Nishi, Eric R. Prossnitz, Mitsuhiro Kawata

    NEUROSCIENCE LETTERS   441 ( 1 )   94 - 99   2008年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER IRELAND LTD  

    Although the expression and distribution of nuclear estrogen receptors in the hippocampus has been described, it has been proposed that the nuclear receptors may not explain all aspects of estrogen function in the hippocampus. Recently, a G protein-coupled receptor for estrogen, GPR30, was identified as a membrane-localized estrogen receptor in several cancer cell lines. In this study, we examined the expression and intracellular distribution of GPR30 in the rat hippocampal formation. We found expression of GPR30 in pyramidal cells of CA1-3 and granule cells of the dentate gyrus at both mRNA and protein levels. Specific markers for intracellular organelles and immunoelectron microscopy revealed that GPR30 was mainly localized to the Golgi apparatus and partially in the endoplasmic reticulum of the neuron but could not detect the protein at the cell surface. Expression levels were not different among male, female in proestrus and female in estrus at the adult stage, but were higher in newborn male than newborn female. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

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  • Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing 査読

    Yoshiteru Kajikawa, Toru Morihara, Hirotaka Sakamoto, Ken-Ichi Matsuda, Yasushi Oshima, Atsuhiko Yoshida, Masateru Nagae, Yuji Arai, Mitsuhiro Kawata, Toshikazu Kubo

    JOURNAL OF CELLULAR PHYSIOLOGY   215 ( 3 )   837 - 845   2008年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Circulation-derived cells play a crucial role in the healing processes of tissue. In early phases of tendon healing processes, circulation-derived cells temporarily exist in the wounded area to initiate the healing process and decrease in number with time. We assumed that a delay of time-dependent decrease in circulation-derived cells could improve the healing of tendons. In this study, we injected platelet-rich plasma (PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and compared the effects on activation of circulation-derived cells and enhancement of tendon healing with a control group (no PRP injection). To follow the circulation-derived cells, we used a green fluorescent protein (GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the numbers of GFP-positive cells and heat-shock protein (HSP47; collagen-specific molecular chaperone)-positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of circulation-derived cells for enhancement of the initial tendon healing process.

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  • Expression, localization and possible actions of 25-Dx, a membraneassociated putative progesterone-binding protein, in the developing Purkinje cell of the cerebellum: a new insight into the biosynthesis, metabolism and multiple actions of progesterone ・・・ 査読

    坂本浩隆, 浮穴和義, 河田光博, 筒井和義

    Cerebellum   7 ( 1 )   18 - 25   2008年3月

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    担当区分:筆頭著者, 責任著者   記述言語:英語  

    Expression, localization and possible actions of 25-Dx, a membraneassociated putative progesterone-binding protein, in the developing Purkinje cell of the cerebellum: a new insight into the biosynthesis, metabolism and multiple actions of progesterone as a neurosteroid

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  • Behavior of host and graft cells in the early remodeling process of rotator cuff defects in a transgenic animal model 査読

    Yoshio Iwata, Toru Morihara, Hisakazu Tachiiri, Yoshiteru Kajikawa, Atsuhiko Yoshida, Yuji Arai, Daisaku Tokunaga, Hirotaka Sakamoto, Ken-ichi Matsuda, Masao Kurokawa, Mitsuhiro Kawata, Toshikazu Kubo

    JOURNAL OF SHOULDER AND ELBOW SURGERY   17 ( 1 )   101S - 107S   2008年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MOSBY-ELSEVIER  

    Autologous tissue graft is one of the treatment options for a large rotator cuff defect. To develop appropriate strategies for enhanced solid graft integration at the bone-tendon interface and tendon-tendon interface, clarifying the fate of the graft and host cells that contribute to repair and remodeling is necessary. We have developed a new grafting model using green fluorescent protein-transgenic rats and wild-type rats to simulate autologous transplantation for examining the behavior of the host and graft cells in the remodeling process after tendon grafting. We found that the host cells commenced proliferation in the graft at 1 day after grafting. The host cells infiltrated into the graft from the subacromial synovium, proximal tendon, and bone-tendon insertion. The number of graft-derived cells decreased with time. Our result clearly demonstrated that host cells, rather than graft cells, were essential for rotator cuff remodeling after tendon grafting for rotator cuff defect.

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  • Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing purkinje cell 査読

    Katsunori Sasahara, Hanako Shikimi, Shogo Haraguchi, Hirotaka Sakamoto, Shin-ichiro Honda, Nobuhiro Harada, Kazuyoshi Tsutsui

    JOURNAL OF NEUROSCIENCE   27 ( 28 )   7408 - 7417   2007年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC NEUROSCIENCE  

    Neurosteroids are synthesized de novo from cholesterol in the brain. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently, we identified the Purkinje cell as an active neurosteroidogenic cell. In rodents, this neuron actively produces several neurosteroids including estradiol during neonatal life, when cerebellar neuronal circuit formation occurs. Estradiol may be involved in cerebellar neuronal circuit formation through promoting neuronal growth and neuronal synaptic contact, because the Purkinje cell expresses estrogen receptor-beta (ER beta). To test this hypothesis, in this study we examined the effects of estradiol on dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell using neonatal wild-type (WT) mice or cytochrome P450 aromatase knock-out (ArKO) mice. Administration of estradiol to neonatal WT or ArKO mice increased dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell. In contrast, WT mice treated with tamoxifen, an ER antagonist, or ArKO mice exhibited decreased Purkinje dendritic growth, spinogenesis, and synaptogenesis at the same neonatal period. To elucidate the mode of action of estradiol, we further examined the expression of brain-derived neurotrophic factor ( BDNF) in response to estrogen actions in the neonate. Estrogen administration to neonatal WT or ArKO mice increased the BDNF level in the cerebellum, whereas tamoxifen decreased the BDNF level in WT mice similar to ArKO mice. BDNF administration to tamoxifen-treated WT mice increased Purkinje dendritic growth. These results indicate that estradiol induces dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell via BDNF action during neonatal life.

    DOI: 10.1523/JNEUROSCI.0710-07.2007

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  • GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing 査読

    Yoshiteru Kajikawa, Toru Morihara, Nobuyoshi Watanabe, Hirotaka Sakamoto, Ken-Ichi Matsuda, Masashi Kobayash, Yasushi Oshima, Atsuhiko Yoshida, Mitsuhiro Kawata, Toshikazu Kubo

    JOURNAL OF CELLULAR PHYSIOLOGY   210 ( 3 )   684 - 691   2007年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    The healing of an injured musculoskeletal system requires an influx of mesenchymal cells that can differentiate into osteoblasts, fibroblasts, chondroblasts, and skeletal myoblasts. However, whether these mesenchymal cells arise from the circulation (bone marrow) or the injured tissues themselves has been controversial. To reveal the spatiotemporal characteristics of the reparative mesenchymal cells, we investigated the healing process after patellar tendon injury using two types of green fluorescent protein (GFP) chimeric rats; one expressing GFP in the circulating cells, and the other expressing it in the patellar tendon. We analyzed the behavior of GFP-positive cells after experimental tendon injury in both chimeric rats to clarify the origin of reparative cells. At 24 h after the injury, the wound contained circulation-derived cells but not tendon-derived cells. Tendon-derived cells first appeared in the wounded area at 3 days after the injury, and had significantly increased in number with time and had maintained a high level of proliferative activity until 7 days after the injury, whereas the circulation-derived cells had decreased in number and had been replaced by the tendon-derived cells. These findings suggest that circulation-derived and tendon-derived cells contribute to the healing of tendons in different periods as part of a biphasic process.

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  • Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres 査読

    Masateru Nagae, Takumi Ikeda, Yasuo Mikami, Hitoshi Hase, Hitoshi Ozawa, Ken-Ichi Matsuda, Hirotaka Sakamot, Yasuhiko Tabata, Mitsuhiro Kawata, Toshikazu Kubo

    TISSUE ENGINEERING   13 ( 1 )   147 - 158   2007年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MARY ANN LIEBERT INC  

    This study evaluated the regenerative effects of platelet-rich plasma (PRP) for the degenerated intervertebral disc (IVD) in vivo. After induction of IVD degeneration in rabbits, we prepared PRP by centrifuging blood obtained from these rabbits. These PRP were injected into the nucleus pulposus (NP) of the degenerated IVDs after impregnation into gelatin hydrogel microspheres that can immobilize PRP growth factors physiochemically and release them in a sustained manner with the degradation of the microspheres. As controls, microspheres impregnated with phosphate-buffered saline (PBS) and PRP without microspheres were similarly injected. Histologically, notable progress in IVD degeneration with time courses was observed in the PBS control, PRP-only, and sham groups. In contrast, progress was remarkably suppressed over the 8-week period in the PRP group. Moreover, in immunohistochemistry, intense immunostaining for proteoglycan in the NP and inner layer of the annulus fibrosus was observed 8 weeks after administration of PRP-impregnated microspheres. Almost all microspheres were indistinct 8 weeks after the injection, and there were no apparent side effects in this study. Our results suggest that the combined administration of PRP and gelatin hydrogel microspheres into the IVD may be a promising therapeutic modality for IVD degeneration.

    DOI: 10.1089/ten.2006.0042

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  • Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain 査読

    M Pei, K Matsuda, H Sakamoto, M Kawata

    EUROPEAN JOURNAL OF NEUROSCIENCE   23 ( 5 )   1234 - 1240   2006年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BLACKWELL PUBLISHING  

    Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17 beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17 beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.

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  • Stress and corticosteroid receptors 査読

    Mitsuhiro Kawata, Mayumi Nishi, Ken-Ichi Matsuda, Hirotaka Sakamoto, Cui Honghai, Takanori Yoshii

    PTSD: Brain Mechanisms and Clinical Implications   29 - 36   2006年

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    記述言語:英語   掲載種別:論文集(書籍)内論文   出版者・発行元:Springer Japan  

    The hypothalamo-pituitary-adrenal (HPA) axis is the main hormonal system involvedin stress response. Neurons in the hypothalamic paraventricular nucleus secreteadrenocorticotrophic hormone-releasing hormone (CRF) and vasopressin,which then synergistically induce the secretion of adrenocorticotrophic hormone(ACTH) from corticotrophs in the anterior pituitary, activating the secretion of theglucocorticoids from the adrenal cortex. Glucocorticoids (Cortisol in human andcorticosterone in rodents) readily enter the brain from the circulating blood andbind to their receptors to induce the secretion of CRF and ACTH for feedback regulationto keep homeostasis through the HPA axis. Over the past decades there hasbeen increasing evidence supporting a critical role for the hippocampus in stressresponse (McEwen 1999). Neurons in the hippocampus express receptors for circulatingglucocorticoids, and animal models of repeated stress caused dendritic atrophyin CAS pyramidal neurons (Woolley et al. 1990
    Watanabe et al. 1992
    Magarinosand McEwen 1995
    Sousa et al. 2000). In the primate prominent pyramidalneuron examples of damage such as dendritic atrophy and pyknotic changes wereobserved in the CAS area of animals subjected to repeated social stress and longtermtreatment of Cortisol (Uno et al. 1989, Sapolsky et al. 1990). These results suggestthat dendritic atrophy of the pyramidal neurons may be one of the factors contributingto the clinically observed decrease of hippocampal volume in humans sufferingfrom stress-related disorders including the posttraumatic stress disorder(PTSD) (Bremner et al. 1995). Transsynaptic inhibitory projection of the hippocampusto hypothalamic paraventricular nucleus has been demonstrated. Therefore, thehippocampus has been the focus of the stress response not only due to its susceptibilityto stress-related damages but also to its negative feedback regulation of thestress response via the HPA axis (Herman and Cullinan 1997). In contrast to thehippocampus, little has been known about how stress affects the amygdala and thenature of its role in the stress response. Recent evidence has demonstrated that theamygdala also plays a critical role in stress response and activation of the HPA axis(Le Doux 1994). It has been suggested that hippocampal plasticity mediates cogni-tive aspects of behavioral impairments caused by stress, whereas changes in theamygdala are more likely to contribute to the affective aspects of stress disorderswith memory consolidation.

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  • Dendritic growth in response to environmental estrogens in the developing Purkinje cell in rats 査読

    H Shikimi, H Sakamoto, Y Mezaki, K Ukena, K Tsutsui

    NEUROSCIENCE LETTERS   364 ( 2 )   114 - 118   2004年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The cerebellar Purkinje cell is a major site for neurosteroid formation. We have demonstrated recently that the Purkinje cell actively produces sex steroids, such as estradiol and progesterone, de novo from cholesterol only during rat neonatal life, when cerebellar cortical formation occurs. We have further demonstrated that both estradiol and progesterone promote the growth of Purkinje cells through intranuclear receptor-mediated mechanisms during cerebellar development. On the other hand, environmental estrogens, such as octylphenol (OP), bisphenol A (BPA), and nonylphenol (NP) are thought to mimic the action of estrogen in the developing central nervous system. Therefore, in this study, the effect of these environmental estrogens on the growth of Purkinje cells was examined in vivo using newborn rats. OP and BPA promoted a dose-dependent dendritic outgrowth of the Purkinje cell but did not affect its soma and cell number. The stimulatory effect of OP and BPA on Purkinje dendritic growth was induced by an injection of 500 mug/day into the cerebrospinal fluid for 4 days and blocked by the estrogen receptor antagonist tamoxifen. However, there was no significant effect of NP on any Purkinje cell morphology. These results suggest that the environmental estrogens, OP and BPA, promote Purkinje dendritic growth during neonatal life. This effect may be mediated by estrogen receptor in the Purkinje cell. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

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  • Organizing actions of neurosteroids in the Purkinje neuron 査読

    K Tsutsui, H Sakamoto, H Shikimi, K Ukena

    NEUROSCIENCE RESEARCH   49 ( 3 )   273 - 279   2004年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    It is becoming clear that steroids can be synthesized de novo by the brain of vertebrates. Such steroids synthesized de novo in the brain, as well as other areas of the nervous system, are called neurosteroids. To understand neurosteroid actions in the brain, we need data on the specific biosynthesis in particular sites of the brain at particular times. Therefore our studies for this exciting area of neuroscience research have focused on the biosynthesis and action of neurosteroids in the identified neurosteroidogenic cells underlying important brain functions. We have demonstrated that the Purkinje cell, a typical cerebellar neuron, is a major site for neurosteroid formation in the brain. This neuron actively synthesizes progesterone and estradiol de novo from cholesterol only during neonatal life, when cerebellar cortical formation occurs dramatically. This is the first observation of neuronal neurosteroidogenesis in the brain. Subsequently the actions of progesterone and estradiol during cerebellar development have become clear by a series of our studies using an excellent Purkinje cellular model. These neurosteroids promote dendritic growth, spinogenesis and synaptogenesis via each receptor in the Purkinje cell. Here we summarize the advances made in our understanding of organizing actions of neurosteroids in the Purkinje cell, an important brain neuron. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

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  • Synapse formation in response to estrogen synthesized de novo in the developing Purkinje cell.

    H. Shikimi, H. Sakamoto, K. Ukena, K. Tsutsui

    In: Trends in Comparative Endocrinology,   319 - 321   2004年

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  • Dendritic growth and spine formation in response to estrogen in the developing Purkinje cell 査読

    H Sakamoto, Y Mezaki, H Shikimi, K Ukena, K Tsutsui

    ENDOCRINOLOGY   144 ( 10 )   4466 - 4477   2003年10月

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    担当区分:筆頭著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ENDOCRINE SOC  

    Neurosteroids are synthesized de novo in the brain, and the cerebellar Purkinje cell is a major site for neurosteroid formation. We have demonstrated that the Purkinje cell possesses intranuclear receptor for progesterone and actively produces progesterone de novo from cholesterol only during rat neonatal life, when cerebellar cortical formation occurs dramatically. We have further demonstrated that progesterone promotes dendritic growth, spinogenesis, and synaptogenesis via its receptor in this neuron in the neonate. On the other hand, estrogen may also play an important role in the process of cerebellar cortical formation, because the neonatal rat Purkinje cell possesses estrogen receptor (ER) beta. However, estrogen formation in the neonatal cerebellum is still unclear. In this study, we therefore analyzed the biosynthesis and action of estrogen in Purkinje cells during neonatal life. RT-PCR-Southern and in situ hybridization analyses showed that Purkinje cells expressed the key enzyme of estrogen formation, cytochrome P450 aromatase, in neonatal rats. A specific enzyme immunoassay for estradiol further indicated that cerebellar estradiol concentrations in the neonate were significantly higher than those in the prepuberty and adult. Both in vitro and in vivo studies with newborn rats showed that estradiol promoted dose-dependent dendritic growth of Purkinje cells. Estradiol also increased the density of Purkinje dendritic spines. These effects were inhibited by the ER antagonist tamoxifen. These results suggest that estradiol in the developing Purkinje cell promotes dendritic growth and spinogenesis via ERbeta in this neuron. Estradiol as well as progesterone may contribute to the growth of Purkinje cells during the cerebellar cortical formation.

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  • Biosynthesis and action of neurosteroids in the cerebellar Purkinje neuron 査読

    K Tsutsui, H Sakamoto, K Ukena

    JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY   85 ( 2-5 )   311 - 321   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The brain is considered to be a target site of peripheral steroid hormones. In contrast to this classical concept, new findings over the past decade have established that the brain itself also synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain, as well as other areas of the nervous system, are called neurosteroids. To understand neurosteroid actions in the brain, we need data on the specific synthesis in particular sites of the brain at particular times. Therefore, our studies for this exciting area of brain research have focused on the biosynthesis and action of neurosteroids in the identified neurosteroidogenic cells underlying important brain functions. We have demonstrated that the Purkinje cell, a typical cerebellar neuron, is a major site for neurosteroid formation in the brain. This is the first observation of neuronal neurosteroidogenesis in the brain. Subsequently, genomic and nongenomic actions of neurosteroids have become clear by a series of our studies using an excellent Purkinje cellular model. On the basis of these findings, we summarize the advances made in our understanding of biosynthesis and action of neurosteroids in the cerebellar Purkinje cell. (C) 2003 Elsevier Ltd. All rights reserved.

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  • Neonatal expression of progesterone receptor isoforms in the cerebellar Purkinje cell in rats 査読

    H Sakamoto, H Shikimi, K Ukena, K Tsutsui

    NEUROSCIENCE LETTERS   343 ( 3 )   163 - 166   2003年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation. Progesterone synthesized de novo in developing PCs participates in the promotion of dendritic growth, spinogenesis and synaptogenesis in this neuron and such organizing actions may contribute to the formation of the cerebellar neuronal circuit during rat neonatal life. Progesterone receptors (PR) occur as two isoforms (PR-A and PR-B) derived from a single gene. To clarify the mode of organizing actions of progesterone, therefore, we examined the expression of these PR isoforms in the rat cerebellum during development. Western immunoblot analysis revealed that both PR isoforms were expressed highly in the cerebellum during neonatal life and the expression decreased thereafter. PR-like immunoreactivity was localized primarily in PCs in the neonatal cerebellum. Thus, progesterone may act directly on PCs via PR isoforms to promote its dendritic growth, spinogenesis and synaptogenesis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

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  • A novel aspect of the cerebellum: biosynthesis of neurosteroids in the Purkinje cell 査読

    K Tsutsui, H Sakamoto, K Ukena

    CEREBELLUM   2 ( 3 )   215 - 222   2003年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:TAYLOR & FRANCIS LTD  

    Peripheral steroid hormones act on brain tissues through intracellular receptor-mediated mechanisms to regulate several important brain neuronal functions. The brain is therefore considered to be a target site of steroid hormones. In contrast to this classical concept, new findings over the past decade have established that the brain itself also synthesizes steroids de novo from cholesterol through mechanisms at least partly independent of peripheral steroidogenic glands. Such steroids synthesized de novo in the brain, as well as other areas of the nervous system, are called neurosteroids. To analyze neurosteroid actions in the brain, we need data on the specific synthesis in particular sites of the brain at particular times. Such information is crucial to developing hypotheses predicting the potential roles of particular neurosteroids in the developing and adult brains. Thus our studies for this exciting area of brain research have focused on the biosynthesis of neurosteroids in the identified neurosteroidogenic cells underlying important brain functions. We have demonstrated that the Purkinje cell, a typical cerebellar neuron, is a major site for neurosteroid formation in the brain. This is the first observation of neuronal neurosteroidogenesis in the brain. Subsequently genomic and nongenomic actions of neurosteroids have been suggested by a series of our studies using an excellent Purkinje cellular model. Here we summarize the advances made in our understanding of biosynthesis of neurosteroids in the cerebellar Purkinje cell.

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  • 総説:ニューロンが合成するニューロステロイドのノンゲノミック作用とゲノミック作用

    筒井和義, 坂本浩隆, 食見花子, 浮穴和義

    生殖内分泌学会雑誌   8   19 - 26   2003年

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    記述言語:日本語  

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  • 総説:ニューロステロイドのシナプス形成誘導作用

    筒井和義, 坂本浩隆, 浮穴和義, 古川康雄

    生体の科学   54   101 - 108   2003年

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    記述言語:日本語  

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  • Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats 査読

    H Sakamoto, K Ukena, K Tsutsui

    NEUROSCIENCE LETTERS   322 ( 2 )   111 - 115   2002年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation. We have demonstrated that this neuron possesses intranuclear receptor for progesterone and actively synthesizes progesterone de novo from cholesterol only during rat neonatal life, when the formation of the cerebellar cortex occurs dramatically. In this study, we therefore analyzed the effect of progesterone on dendritic spine formation of the PC. In vitro studies using cerebellar slice cultures from newborn rats showed that progesterone increases the density of PC dendritic spines in a dose-dependent manner. This effect was blocked by the progesterone receptor antagonist, RU486. Furthermore, trilostane, a specific inhibitor of progesterone synthesis, inhibited the increase of spine density. These results suggest that progesterone can promote dendritic spine formation, and endogenous progesterone synthesized de novo in the developing PC may induce such an effect. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

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  • Novel cerebellar function: Neurosteroids in the purkinje neuron and their genomic and nongenomic actions

    K Tsutsui, K Ukena, H Sakamoto

    NEUROPLASTICITY, DEVELOPMENT, AND STEROID HORMONE ACTION   101 - 116   2002年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:CRC PRESS-TAYLOR & FRANCIS GROUP  

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  • Activity and localization of 3 beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4)-isomerase in the zebrafish central nervous system 査読

    H Sakamoto, K Ukena, K Tsutsui

    JOURNAL OF COMPARATIVE NEUROLOGY   439 ( 3 )   291 - 305   2001年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:WILEY-LISS  

    Little information is available for neurosteroidogenesis in the central nervous system (CNS) of lower vertebrates. Therefore, in the present study, we examined the enzymatic activity and localization of 3 beta -hydroxysteroid dehydrogenase/Delta (5)-Delta (4)-isomerase (3 beta HSD), a key steroidogenic enzyme, in the CNS of adult male zebrafish to clarify central progesterone biosynthesis. Biochemical studies together with HPLC analysis revealed that the zebrafish brain converted pregnenolone to progesterone, suggesting the enzymatic activity of 3 beta HSD. This conversion was significantly reduced by trilostane, a specific inhibitor of 3 beta HSD. By using Western immunoblotting with the polyclonal. antiserum. directed against purified bovine adrenal 3 beta HSD, a 3 beta HSD-like substance was found in homogenates of the zebrafish brain. Immunocytochemical analysis was then undertaken to investigate the localization of the 3 beta HSD-like substance in the zebrafish brain and spinal cord. Clusters of immunoreactive cell bodies were localized in the dorsal telencephalic. areas (D), central posterior thalamic nucleus (CP), preoptic nuclei (NPO), posterior tuberal nucleus (PTN), paraventricular organ (PVO), and nucleus of medial longitudinal fascicle (NMLF). 3 beta HSD-like immunoreactivity was also observed in somata of cerebellar Purkinje neurons. A widespread distribution of immunoreactive fibers was found throughout the brain and spinal cord. In addition, positively stained cells were restricted to other organs, such as the pituitary and retina. Preabsorbing the antiserum with purified bovine adrenal microsome resulted in a complete absence of 3 beta HSD-like immunoreactivity. These results suggest that the fish CNS possesses steroidogenic enzyme 3 beta HSD and produces progesterone. The present study further provides the first immunocytochemical mapping of the site of 3 beta HSD expression in the fish CNS. (C) 2001 Wiley-Liss, Inc.

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  • Developmental changes in galanin in lumbosacral sympathetic ganglionic neurons innervating the avian uterine oviduct and galanin induction by sex steroids 査読

    T Ubuka, H Sakamoto, D Li, K Ukena, K Tsutsui

    JOURNAL OF ENDOCRINOLOGY   170 ( 2 )   357 - 368   2001年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:SOC ENDOCRINOLOGY  

    We recently found lumbosacral sympathetic ganglionic galanin neurons innervating the quail uterine oviduct. Galaninergic innervation of the uterine muscle may be essential for avian oviposition, as galanin evoked oviposition through a mechanism of induction of vigorous uterine contraction. The questions arising from these findings are: what changes occur in galanin expression in the sympathetic ganglionic galanin neuron during development, and what is the hormonal Factor(s) that induces galanin expression in this neuron? Therefore, the present study examined the developmental changes in galanin of the quail sympathetic ganglionic neuron and uterus, and the effect of administration of ovarian sex steroids on galanin induction. Immature birds reared under long-day photoperiods from 4 weeks of age demonstrated progressive increases in galanin levels both per unit ganglionic protein (concentration) and per ganglia (content) concurrent with ganglionic development during weeks 4-13. The uterine galanin content and uterine weight also increased progressively during the same period, but the galanin concentration in the uterus at 4 weeks was high due to the much smaller tissue mass. Immunocytochemical analysis with anti-galanin serum showed that immunoreactive ganglionic cells were few and small at 4 weeks and increased progressively thereafter. Administration of oestradiol-17 beta to immature birds at 3 weeks of age for I week increased both the galanin concentration and content in the ganglia without ganglionic growth. A marked increase in galanin-immunoreactive ganglionic cells was detected following oestradiol treatment. In contrast, progesterone increased ganglionic galanin levels, but the effects were low. Expression of the mRNAs encoding oestrogen receptor-alpha and -beta (ER alpha and ER beta) in the ganglionic tissue was verified by RT-PCR/Southern blot analysis. Immunocytochemical staining with anti-ER serum further revealed an intense immunoreaction restricted to the nucleus of ganglionic neurons.
    These results suggest that ovarian sex steroids, in particular oestradiol-17 beta, contribute as hormonal factors to galanin induction, which takes place in the lumbosacral sympathetic ganglionic neurons innervating avian uterine oviduct during development. Oestradiol may act directly on this ganglionic neuron through intra-nuclear receptor-mediated mechanisms to induce galanin.

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  • Sympathetic ganglionic galanin neurons evoke avian oviposition by innervating the uterine oviduct: A novel neuronal mechanism of avian oviposition

    H Sakamoto, T Ubuka, C Kohchi, K Ukena, K Tsutsui

    PERSPECTIVE IN COMPARATIVE ENDOCRINOLOGY: UNITY AND DIVERSITY   647 - 653   2001年

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)   出版者・発行元:MEDIMOND S R L  

    We recently isolated an oviposition-inducing peptide that was identified as avian galanin from mature quail uterine oviducts. This peptide was localized in neuronal fibers terminating in the uterus, and its receptors were also observed in the uterus. To understand the control mechanism of avian oviposition by galanin, we identified the neurons that synthesize galanin and project to the uterus in mature quails. Retrograde labeling with neurobiotin from the uterus revealed that lumbosacral sympathetic ganglionic neurons projected to the uterine muscle. Colocalization of neurobiotin with galanin-like substance was further confirmed by the ultrastructural immunocytochemistry. Expressions of galanin and its mRNA in the neurons were further confirmed by competitive enzyme-linked immunosorbent assay and Northern blot analysis. These results suggest that lumbosacral sympathetic ganglionic neurons project to the uterine muscle and produce galanin in mature quails.

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  • Novel brain function: biosynthesis and actions of neurosteroids in neurons 査読

    K Tsutsui, K Ukena, M Usui, H Sakamoto, M Takase

    NEUROSCIENCE RESEARCH   36 ( 4 )   261 - 273   2000年4月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Peripheral steroid hormones act on brain tissues through intracellular receptor-mediated mechanisms to regulate several important brain neuronal functions. Therefore, the brain is considered to be a target site of steroid hormones. However, it is now established that the brain itself also synthesizes steroids de novo from cholesterol. The pioneering discovery of Baulicu and his colleagues, using mammals, and our studies with non-mammals have opened the door of a new research field. Such steroids synthesized in the brain are called neurosteroids. Because certain structures in vertebrate brains have the capacity to produce neurosteroids identification of neurosteroidogenic cells in the brain is essential to understand the physiological role of neurosteroids in brain functions. Glial cells are generally accepted to be the major site for neurosteroid formation. but the concept of neurosteroidogenesis in brain neurons has up to now been uncertain. We recently demonstrated neuronal neurosteroidogenesis in the blain and indicated that the Purkinje cell, a typical cerebellar neuron, actively synthesizes several neurosteroids de novo from cholesterol in both mammals and non-mammals. Pregnenolone sulfate, one of neurosteroids synthesized in the Purkinje neuron, may contribute to some important events in the cerebellum by modulating neurotransmission. Progesterone, produced as a neurosteroid in this neuron only during neonatal life, may be involved in the promotion of neuronal and glial growth and neuronal synaptic contact ill the cerebellum. More recently, biosynthesis and actions of neurosteroids in pyramidal neurons of the hippocampus were also demonstrated. These serve an excellent model for the study of physiological roles of neurosteroids in the brain, because both cerebellar Purkinje neurons and hippocampal neurons play an important role in memory and learning. This paper summarizes the advances made in our understanding of neurosteroids, produced in neurons, and their actions. (C) 2000 Elsevier Science ireland Ltd and the Japan Neuroscience Society. All rights reserved.

    DOI: 10.1016/S0168-0102(99)00132-7

    DOI: 10.1016/s0168-0102(99)00132-7

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    その他リンク: http://orcid.org/0000-0002-6224-4591

  • 総説 : 神経ステロイドによるシナプス可塑性調節

    筒井和義, 浮穴和義, 坂本浩隆

    特集:脳のシナプス Brain Medical   12   298 - 306   2000年

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  • Posthatching development of spinal motoneurons in the angelfish Pterophyllum scalare 査読

    M Yoshida, M Fudoji, H Sakamoto, K Uematsu

    BRAIN BEHAVIOR AND EVOLUTION   53 ( 4 )   180 - 186   1999年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    We investigated the posthatching developmental sequence of spinal motoneurons innervating the axial muscles in the teleost angelfish, Pterophyllum scalare, by means of retrograde labeling with horseradish peroxidase. Two discrete types of spinal motoneurons, primary-type motoneurons and secondary motoneurons were labeled in a temporally different sequence during the course of larval development. These two types of motoneurons were morphologically distinguishable from one other. Primary-type motoneurons are generated by day 1 posthatching and do not increase in number over the observed period (to day 12 posthatching). In contrast, the secondary motoneurons increase in number through posthatching day 3. Differentiation of the spinal motoneurons appears to be nearly complete a few days before the onset of free swimming. In addition, the data suggest that the differentiation of secondary motoneurons precedes the development of the red muscle that is to be innervated by the motoneurons.

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▼全件表示

書籍等出版物

  • 基礎生物科学

    培風館  2016年 

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  • 雄の性機能をつかさどる脳-脊髄神経回路の解明

    株式会社クバプロ  2013年 

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  • Neurobiology of Post-traumatic Stress Disorder

    2009年 

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  • 栄養科学シリーズNEXT 解剖生理学 人体の構造と機能 第2版

    講談社サイエンティフィック  2008年 

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  • PTSD-Brain Mechanisms and Clinical Implications

    Spring Verlag  2006年 

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MISC

  • 'Central' Actions of Corticosteroid Signaling Suggested by Constitutive Knockout of Corticosteroid Receptors in Small Fish. 国際誌

    Tatsuya Sakamoto, Hirotaka Sakamoto

    Nutrients   11 ( 3 )   2019年3月

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    記述言語:英語  

    This review highlights recent studies of the functional implications of corticosteroids in some important behaviors of model fish, which are also relevant to human nutrition homeostasis. The primary actions of corticosteroids are mediated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which are transcription factors. Zebrafish and medaka models of GR- and MR-knockout are the first constitutive corticosteroid receptor-knockout animals that are viable in adulthood. Similar receptor knockouts in mice are lethal. In this review, we describe the physiological and behavioral changes following disruption of the corticosteroid receptors in these models. The GR null model has peripheral changes in nutrition metabolism that do not occur in a mutant harboring a point mutation in the GR DNA-binding domain. This suggests that these are not "intrinsic" activities of GR. On the other hand, we propose that integration of visual responses and brain behavior by corticosteroid receptors is a possible "intrinsic"/principal function potentially conserved in vertebrates.

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  • Early-life exposure to Tris(1,3-dichloroisopropyl) phosphate induces dose-dependent suppression of sexual behavior in male rats. 国際誌

    Manami Kamishima, Tatsuya Hattori, Go Suzuki, Hidenori Matsukami, Chiaki Komine, Yasuyuki Horii, Gen Watanabe, Takumi Oti, Hirotaka Sakamoto, Tomoko Soga, Ishwar S Parhar, Yasuhiko Kondo, Hidetaka Takigami, Maiko Kawaguchi

    Journal of applied toxicology : JAT   38 ( 5 )   649 - 655   2018年5月

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    記述言語:英語  

    Exposure to endocrine-disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti-androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25-250 mg kg-1 via oral administration over 28 consecutive days post-birth) suppressed male sexual behavior and reduced testes size. These changes were dose-dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life.

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  • Analyzing the effects of co-expression of chick (Gallus gallus) melanocortin receptors with either chick MRAP1 or MRAP2 in CHO cells on sensitivity to ACTH(1-24) or ACTH(1-13)NH2: implications for the HPA axis and melanocortin circuits in the hypothal・・・

    Thomas AL, Maekawa F, Kawashima T, Sakamoto H, Sakamoto T, Davis P, Dores RM

    General and Comparative Endocrinology   256   50 - 56   2018年1月

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    記述言語:英語  

    Analyzing the effects of co-expression of chick (Gallus gallus) melanocortin receptors with either chick MRAP1 or MRAP2 in CHO cells on sensitivity to ACTH(1-24) or ACTH(1-13)NH2: implications for the HPA axis and melanocortin circuits in the hypothalamus of the chick

    DOI: 10.1016/j.ygcen.2017.09.002

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  • Identification of the sexually dimorphic gastrin-releasing peptide system in the lumbosacral spinal cord that controls male reproductive function in the mouse and Asian house musk shrew (Suncus murinus)

    Kei Tamura, Yasuhisa Kobayashi, Asuka Hirooka, Keiko Takanami, Takumi Oti, Takamichi Jogahara, Sen-ichi Oda, Tatsuya Sakamoto, Hirotaka Sakamoto

    JOURNAL OF COMPARATIVE NEUROLOGY   525 ( 7 )   1586 - 1598   2017年5月

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    記述言語:英語   出版者・発行元:WILEY  

    Several regions of the brain and spinal cord control male reproductive function. We previously demonstrated that the gastrin-releasing peptide (GRP) system, located in the lumbosacral spinal cord of rats, controls spinal centers to promote penile reflexes during male copulatory behavior. However, little information exists on the male-specific spinal GRP system in animals other than rats. The objective of this study was to examine the functional generality of the spinal GRP system in mammals using the Asian house musk shrew (Suncus murinus; suncus named as the laboratory strain), a specialized placental mammal model. Mice are also used for a representative model of small laboratory animals. We first isolated complementary DNA encoding GRP in suncus. Phylogenetic analysis revealed that suncus preproGRP was clustered to an independent branch. Reverse transcription-PCR showed that GRP and its receptor mRNAs were both expressed in the lumbar spinal cord of suncus and mice. Immunohistochemistry for GRP demonstrated that the sexually dimorphic GRP system and male-specific expression/distribution patterns of GRP in the lumbosacral spinal cord in suncus are similar to those of mice. In suncus, we further found that most GRP-expressing neurons in males also express androgen receptors, suggesting that this male-dominant system in suncus is also androgen-dependent. Taken together, these results indicate that the sexually dimorphic spinal GRP system exists not only in mice but also in suncus, suggesting that this system is a conserved property in mammals. J. Comp. Neurol. 525:1586-1598, 2017. (c) 2016 Wiley Periodicals, Inc.

    DOI: 10.1002/cne.24138

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  • ヒメダカの三角関係(雄、雄、雌)における勝者を決めるホルモン 招待

    横井佐織, 坂本竜哉, 坂本浩隆, 竹内秀明

    海洋と生物   37 ( 6 )   591 - 597   2015年12月

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    記述言語:日本語   掲載種別:記事・総説・解説・論説等(商業誌、新聞、ウェブメディア)  

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  • 超高圧電子顕微鏡・トモグラフィー法を用いた脊髄内痒み神経ネットワークの解析

    坂本浩隆, 佐藤慧太, 高浪景子, 高浪景子, 高浪景子, 村田和義, 河田光博, 坂本竜哉

    日本内分泌学会雑誌   91 ( 2 )   525 - 525   2015年9月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • In vivo imaging of axonal transport of mitochondria in the diseased and aged mammalian CNS

    Yuji Takihara, Masaru Inatani, Kei Eto, Toshihiro Inoue, Alexander Kreymerman, Seiji Miyake, Shinji Ueno, Masatoshi Nagaya, Ayami Nakanishi, Keiichiro Iwao, Yoshihiro Takamura, Hirotaka Sakamoto, Keita Satoh, Mineo Kondo, Tatsuya Sakamoto, Jeffrey L. Goldberg, Junichi Nabekura, Hidenobu Tanihara

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   112 ( 33 )   10515 - 10520   2015年8月

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    記述言語:英語   出版者・発行元:NATL ACAD SCIENCES  

    The lack of intravital imaging of axonal transport of mitochondria in the mammalian CNS precludes characterization of the dynamics of axonal transport of mitochondria in the diseased and aged mammalian CNS. Glaucoma, the most common neurodegenerative eye disease, is characterized by axon degeneration and the death of retinal ganglion cells (RGCs) and by an age-related increase in incidence. RGC death is hypothesized to result from disturbances in axonal transport and in mitochondrial function. Here we report minimally invasive intravital multiphoton imaging of anesthetized mouse RGCs through the sclera that provides sequential time-lapse images of mitochondria transported in a single axon with submicrometer resolution. Unlike findings from explants, we show that the axonal transport of mitochondria is highly dynamic in the mammalian CNS in vivo under physiological conditions. Furthermore, in the early stage of glaucoma modeled in adult (4-mo-old) mice, the number of transported mitochondria decreases before RGC death, although transport does not shorten. However, with increasing age up to 23-25 mo, mitochondrial transport (duration, distance, and duty cycle) shortens. In axons, mitochondria-free regions increase and lengths of transported mitochondria decrease with aging, although totally organized transport patterns are preserved in old (23- to 25-mo-old) mice. Moreover, axonal transport of mitochondria is more vulnerable to glaucomatous insults in old mice than in adult mice. These mitochondrial changes with aging may underlie the age-related increase in glaucoma incidence. Our method is useful for characterizing the dynamics of axonal transport of mitochondria and may be applied to other submicrometer structures in the diseased and aged mammalian CNS in vivo.

    DOI: 10.1073/pnas.1509879112

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  • P4-10 医学・生物学分野における超高圧電子顕微鏡・トモグラフィー法の再考 : A revisiting study for 3D-EM(細胞生物・電子顕微鏡,ポスター発表,組織化学のモーダルシフト,第56回日本組織細胞化学会総会・学術集会)

    坂本 浩隆, 佐藤 慧太, 高浪 景子, 村田 和義, 河田 光博, 坂本 竜哉

    日本組織細胞化学会総会プログラムおよび抄録集   ( 56 )   71 - 71   2015年

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    記述言語:日本語   出版者・発行元:日本組織細胞化学会  

    CiNii Article

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  • かゆみを伝える神経ネットワーク

    高浪景子, 坂本浩隆, 宮崎直幸, 村田和義, 佐藤慧太, 坂本竜哉, 谷田任司, 山田俊児, 松田賢一, 河田光博

    日本内分泌学会雑誌   90 ( 2 )   602 - 602   2014年9月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • Bioimaging histochemistry 免疫組織化学法を用いた体性感覚ニューロン系の3次元微細構造解析

    高浪 景子, 坂本 浩隆, 宮崎 直幸, 村田 和義, 佐藤 慧太, 坂本 竜哉, 河田 光博

    日本組織細胞化学会総会・学術集会講演プログラム・予稿集   55回   65 - 65   2014年9月

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    記述言語:日本語   出版者・発行元:日本組織細胞化学会  

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  • Quality Control of Photosystem II: Direct Imaging of the Changes in the Thylakoid Structure and Distribution of FtsH Proteases in Spinach Chloroplasts under Light Stress

    Miho Yoshioka-Nishimura, Daisuke Nanba, Takashi Takaki, Chikako Ohba, Nodoka Tsumura, Noriko Morita, Hirotaka Sakamoto, Kazuyoshi Murata, Yasusi Yamamoto

    PLANT AND CELL PHYSIOLOGY   55 ( 7 )   1255 - 1265   2014年7月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS  

    Under light stress, the reaction center-binding protein D1 of PSII is photo-oxidatively damaged and removed from PSII complexes by proteases located in the chloroplast. A protease considered to be responsible for degradation of the damaged D1 protein is the metalloprotease FtsH. We showed previously that the active hexameric FtsH protease is abundant at the grana margin and the grana end membranes, and this homo-complex removes the photodamaged D1 protein in the grana. Here, we showed a change in the distribution of FtsH in spinach thylakoids during excessive illumination by transmission electron microscopy (TEM) and immunogold labeling of FtsH. The change in distribution of the protease was accompanied by structural changes to the thylakoids, which we detected using spinach leaves by TEM after chemical fixation of the samples. Quantitative analyses showed several characteristic changes in the structure of the thylakoids, including shrinkage of the grana, outward bending of the marginal portions of the thylakoids and an increase in the height of the grana stacks under excessive illumination. The increase in the height of the grana stacks may include swelling of the thylakoids and an increase in the partition gaps between the thylakoids. These data strongly suggest that excessive illumination induces partial unstacking of the thylakoids, which enables FtsH to access easily the photodamaged D1 protein. Finally three-dimensional tomography of the grana was recorded to observe the effect of light stress on the overall structure of the thylakoids.

    DOI: 10.1093/pcp/pcu079

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  • Distribution of Gastrin-Releasing Peptide in the Rat Trigeminal and Spinal Somatosensory Systems

    Keiko Takanami, Hirotaka Sakamoto, Ken Ichi Matsuda, Keita Satoh, Takashi Tanida, Shunji Yamada, Kaihei Inoue, Takumi Oti, Tatsuya Sakamoto, Mitsuhiro Kawata

    JOURNAL OF COMPARATIVE NEUROLOGY   522 ( 8 )   1858 - 1873   2014年6月

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

    Gastrin-releasing peptide (GRP) has recently been identified as an itch-specific neuropeptide in the spinal sensory system in mice, but there are no reports of the expression and distribution of GRP in the trigeminal sensory system in mammals. We characterized and compared GRP-immunoreactive (ir) neurons in the trigeminal ganglion (TG) with those in the rat spinal dorsal root ganglion (DRG). GRP immunoreactivity was expressed in 12% of TG and 6% of DRG neurons and was restricted to the small- and medium-sized type cells. In both the TG and DRG, many GRP-ir neurons also expressed substance P and calcitonin gene-related peptide, but not isolectin B-4. The different proportions of GRP and transient receptor potential vanilloid 1 double-positive neurons in the TG and DRG imply that itch sensations via the TG and DRG pathways are transmitted through distinct mechanisms. The distribution of the axon terminals of GRP-ir primary afferents and their synaptic connectivity with the rat trigeminal sensory nuclei and spinal dorsal horn were investigated by using light and electron microscopic histochemistry. Although GRP-ir fibers were rarely observed in the trigeminal sensory nucleus principalis, oralis, and interpolaris, they were predominant in the superficial layers of the trigeminal sensory nucleus caudalis (Vc), similar to the spinal dorsal horn. Ultrastructural analysis revealed that GRP-ir terminals contained clear microvesicles and large dense-cored vesicles, and formed asymmetric synaptic contacts with a few dendrites in the Vc and spinal dorsal horn. These results suggest that GRP-dependent orofacial and spinal pruriceptive inputs are processed mainly in the superficial laminae of the Vc and spinal dorsal horn. J. Comp. Neurol. 522:1858-1873, 2014. (c) 2013 Wiley Periodicals, Inc.

    DOI: 10.1002/cne.23506

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  • 光化学系IIのquality control:光ストレス下でのホウレンソウ葉緑体のグラナ膜構造の変化

    難波大介, 西村美保, 坂本浩隆, 村田和義, 高木孝士, 山本泰

    日本植物生理学会年会要旨集   55th   328   2014年3月

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  • Identification of CNS Neurons Innervating the Levator Ani and Ventral Bulbospongiosus Muscles in Male Rats

    Amy D. Dobberfuhl, Takumi Oti, Hirotaka Sakamoto, Lesley Marson

    JOURNAL OF SEXUAL MEDICINE   11 ( 3 )   664 - 677   2014年3月

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    記述言語:英語   出版者・発行元:WILEY  

    IntroductionThe pelvic striated muscles play an important role in mediating erections and ejaculation, and together these muscles compose a tightly coordinated neuromuscular system that is androgen sensitive and sexually dimorphic.
    AimTo identify spinal and brains neurons involved in the control of the levator ani (LA) and bulbospongiosus (BS) in the male adult and preadolescent rat.
    MethodsRats were anesthetized, and the transsynaptic retrograde tracer pseudorabies virus (PRV) was injected into the LA muscle of adults or the ventral BS muscle in 30-day-old rats. After 3-5 days rats were sacrificed, and PRV-labeled neurons in the spinal cords and brains were identified using immunohistochemistry. The presence of gastrin-releasing peptide (GRP) in the lumbar spinal neurons was examined.
    Main Outcomes MeasuresThe location and number of PRV-labeled neurons in the spinal cord and brain and GRP colocalization in the lumbar spinal cord.
    ResultsPRV-labeled spinal interneurons were found distributed throughout T11-S1 of the spinal cord, subsequent to dorsal medial motoneuron infection. The majority of spinal interneurons were found in the lumbosacral spinal cord in the region of the dorsal gray commissure and parasympathetic preganglionic neurons. Preadolescent rats had more PRV-labeled spinal interneurons at L5-S1 where the motoneurons were located but relatively less spread rostrally in the spinal cord compared with adults. Lumbar spinothalmic neurons in medial gray of L3-L4 co-localized PRV and GRP. In the brain consistent labeling was seen in areas known to be involved in male sexual behavior including the ventrolateral medulla, hypothalamic paraventricular nucleus, and medial preoptic area.
    ConclusionCommon spinal and brain pathways project to the LA and BS muscles in the rat suggesting that these muscles act together to coordinate male sexual reflexes. Differences may exist in the amount of synaptic connections/neuronal pathways in adolescents compared with adults. Dobberfuhl AD, Oti T, Sakamoto H, and Marson L. Identification of CNS neurons innervating the levator ani and ventral bulbospongiosus muscles in male rats. J Sex Med 2014;11:664-677.

    DOI: 10.1111/jsm.12418

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  • W3-02 免疫組織化学法を用いた体性感覚ニューロン系の3次元微細構造解析(W3 Bioimaging histochemistry,ワークショップ,第55回日本組織細胞化学会総会・学術集会 第11回日中合同組織細胞化学セミナー)

    高浪 景子, 坂本 浩隆, 宮崎 直幸, 村田 和義, 佐藤 慧太, 坂本 竜哉, 河田 光博

    日本組織細胞化学会総会プログラムおよび抄録集   ( 55 )   65 - 65   2014年

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    記述言語:日本語   出版者・発行元:日本組織細胞化学会  

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  • 光化学系IIのquality control:光ストレス下でのホウレンソウ葉緑体チラコイド膜構造変化の電子顕微鏡による観察

    難波大介, 西村美保, 坂本浩隆, 村田和義, 高木孝士, 山本泰

    日本植物学会大会研究発表記録   77th   231   2013年8月

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  • 光化学系IIのquality control:電子顕微鏡を用いた光ストレス下のホウレンソウ葉緑体のグラナチラコイド膜構造の観察

    難波大介, 西村美保, 大庭千加子, 坂本浩隆, 村田和義, 高木孝士, 山本泰

    日本植物生理学会年会要旨集   54th   238   2013年3月

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  • Potential roles of arginine-vasotocin in the regulation of aggressive behavior in the mudskipper (#IPeriophthalmus modestus#IR)

    N. Kagawa

    General and Comparative Endocrinology   194   257 - 263   2013年

  • 超高圧電子顕微鏡を用いたラット脊髄gastrin‐releasing peptide系を中心とした脊髄内局所神経回路の三次元的解析

    越智拓海, 佐藤慧太, 齊藤和裕, 村田和義, 河田光博, 坂本竜哉, 坂本浩隆

    日本解剖学会総会・全国学術集会講演プログラム・抄録集   118th   167   2013年

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  • Potential roles of arginine-vasotocin in the regulation of aggressive behavior in the mudskipper (#IPeriophthalmus modestus#IR)

    N. Kagawa

    General and Comparative Endocrinology   194   257 - 263   2013年

  • Three-dimensional evaluation of the spinal local neural network revealed by the high-voltage electron microscopy: a double immunohistochemical study

    Takumi Oti, Keita Satoh, Kazuhiro Saito, Kazuyoshi Murata, Mitsuhiro Kawata, Tatsuya Sakamoto, Hirotaka Sakamoto

    HISTOCHEMISTRY AND CELL BIOLOGY   138 ( 4 )   693 - 697   2012年10月

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    記述言語:英語   出版者・発行元:SPRINGER  

    Three-dimensional (3-D) analysis of anatomical ultrastructures is important in biological research. However, 3-D image analysis on exact serial sets of ultra-thin sections from biological specimens is very difficult to achieve, and limited information can be obtained by 3-D reconstruction from these sections due to the small area that can be reconstructed. On the other hand, the high-penetration power of electrons by an ultra-high accelerating voltage enables thick sections of biological specimens to be examined. High-voltage electron microscopy (HVEM) is particularly useful for 3-D analysis of the central nervous system because considerably thick sections can be observed at the ultrastructure level. Here, we applied HVEM tomography assisted by light microscopy to a study of the 3-D chemical neuroanatomy of the rat lower spinal cord annotated by double-labeling immunohistochemistry. This powerful methodology is useful for studying molecular and/or chemical neuroanatomy at the 3-D ultrastructural level.

    DOI: 10.1007/s00418-012-0976-6

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  • 光化学系IIのquality control:電子顕微鏡を用いた光ストレス下のホウレンソウ葉緑体のグラナチラコイド膜構造の観察

    難波大介, 西村(吉岡)美保, 坂本浩隆, 村田和義, 山本泰

    日本植物学会大会研究発表記録   76th   222   2012年9月

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  • Brain-spinal cord neural circuits controlling male sexual function and behavior

    Hirotaka Sakamoto

    Neuroscience Research   72 ( 2 )   103 - 116   2012年2月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等  

    Men and women exhibit differences in sexual behavior. This indicates that neural circuits within the central nervous system (CNS) that control sexual behavior differ between the sexes, although differences in behavior are also influenced by sociocultural and hormonal factors. Sexual differentiation of the body and brain occurs during the embryonic and neonatal periods in humans and persists into adulthood with relatively low plasticity. Male sexual behavior is complex and depends on intrinsic and extrinsic factors, including olfactory, somatosensory and visceral cues. Many advances in our understanding of sexually dimorphic neural circuits have been achieved in animal models, but major issues are yet to be resolved. This review summarizes the sexually dimorphic nuclei controlling male sexual function in the rodent CNS and focuses on the interactions of the brain-spinal cord neural networks controlling male sexual behavior. Possible factors that relate findings from animal studies to human behavior are also discussed. © 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society.

    DOI: 10.1016/j.neures.2011.11.002

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  • Hemolymph osmotic, ionic status, and branchial Na<sup>+</sup>/K<sup>+</sup>-ATPase activity under varying environmental conditions in the intertidal grapsid crab, Gaetice depressusd

    Takeshi Nanba, Hideya Takahashi, Tsukasa Abe, Waichirou Godo, Maho Ogoshi, Hirotaka Sakamoto, Naoaki Tsutsui, Tatsuya Sakamoto

    International Aquatic Research   4 ( 1 )   1 - 12   2012年

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    © 2012, Nanba et al.; licensee Springer. Osmo- and ionoregulatory abilities were examined in the intertidal grapsid crab, Gaetice depressus, transferred from normal seawater (30 ppt) to low (10 ppt) or high (50 ppt) salinities for 2 and 10 days, in addition to animals kept out of water for 2 days. The results of the hemolymph osmotic and ionic status indicate that G. depressus is able to adapt for more than 10 days in these salinities and for 2 days under terrestrial conditions. Especially, the free Ca2+ concentration was relatively maintained compared with concentrations of monovalent ions and osmolality values in 10 and 50 ppt, partly using the complexed calcium (total minus free calcium) as an internal reserve in the hemolymph. In 10 ppt, complexed calcium disappeared from the hemolymph after 10 days, indicating that all the hemolymph calcium was ionized. In 50 ppt, free Ca2+ was regulated to lower levels than concentrations in the medium, while total calcium increased to higher levels after 2 days. Examination of Na+/K+-ATPase activity, which has been implicated in ion transport in many crustaceans, revealed that induction of high Na+/K+-ATPase activity varies among the posterior gills in response to salinities. Ten-ppt salinity induces activity in two of the posterior gills (gill numbers 6 and 7, eight in total), albeit with differing degrees of response. In contrast, 50-ppt salinity stimulates the activity primarily in gill number 8, suggesting that this gill may be associated specifically with ion excretion in G. depressus. As a euryhaline amphibious crab, this abundant species around Japan will serve as a model to study the osmotic/ionic regulatory mechanisms which operate in crustaceans.

    DOI: 10.1186/2008-6970-4-18

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  • Achieve orgasm? Oxytocin triggers ejaculation in men

    H. Sakamoto

    Reproductive System & Sexual Disorders   1   e101-e101   2012年

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  • Hemolymph osmotic, ionic status, and branchial Na<sup>+</sup>/K<sup>+</sup>-ATPase activity under varying environmental conditions in the intertidal grapsid crab, Gaetice depressusd

    Takeshi Nanba, Hideya Takahashi, Tsukasa Abe, Waichirou Godo, Maho Ogoshi, Hirotaka Sakamoto, Naoaki Tsutsui, Tatsuya Sakamoto

    International Aquatic Research   4 ( 1 )   1 - 12   2012年

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    © 2012, Nanba et al.; licensee Springer. Osmo- and ionoregulatory abilities were examined in the intertidal grapsid crab, Gaetice depressus, transferred from normal seawater (30 ppt) to low (10 ppt) or high (50 ppt) salinities for 2 and 10 days, in addition to animals kept out of water for 2 days. The results of the hemolymph osmotic and ionic status indicate that G. depressus is able to adapt for more than 10 days in these salinities and for 2 days under terrestrial conditions. Especially, the free Ca2+ concentration was relatively maintained compared with concentrations of monovalent ions and osmolality values in 10 and 50 ppt, partly using the complexed calcium (total minus free calcium) as an internal reserve in the hemolymph. In 10 ppt, complexed calcium disappeared from the hemolymph after 10 days, indicating that all the hemolymph calcium was ionized. In 50 ppt, free Ca2+ was regulated to lower levels than concentrations in the medium, while total calcium increased to higher levels after 2 days. Examination of Na+/K+-ATPase activity, which has been implicated in ion transport in many crustaceans, revealed that induction of high Na+/K+-ATPase activity varies among the posterior gills in response to salinities. Ten-ppt salinity induces activity in two of the posterior gills (gill numbers 6 and 7, eight in total), albeit with differing degrees of response. In contrast, 50-ppt salinity stimulates the activity primarily in gill number 8, suggesting that this gill may be associated specifically with ion excretion in G. depressus. As a euryhaline amphibious crab, this abundant species around Japan will serve as a model to study the osmotic/ionic regulatory mechanisms which operate in crustaceans.

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  • Immunohistochemical Analysis of the Effects of Estrogen on Intraarticular Neurogenic Inflammation in a Rat Anterior Cruciate Ligament Transection Model of Osteoarthritis

    Atsuhiko Yoshida, Toru Morihara, Ken-ichi Matsuda, Hirotaka Sakamoto, Yuji Arai, Yoshikazu Kida, Mitsuhiro Kawata, Toshikazu Kubo

    CONNECTIVE TISSUE RESEARCH   53 ( 3 )   197 - 206   2012年

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    記述言語:英語   出版者・発行元:INFORMA HEALTHCARE  

    Synovitis is considered as one of the factors associated with the pathogenesis of osteoarthritis (OA). There is currently a significant amount of research linking estrogen deficiencies with the development of OA in estrogen-deficient women, including postmenopausal women; however, the exact etiology remains unclear. Various neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been shown to contribute to synovitis in OA joints, and the influence of estrogen on the expressions of SP and CGRP in the synovium of OA joints has been noted. After ovariectomy (OVX) followed by estradiol (E2) replacement, 24 female rats were divided into three groups: OVX group, OVX + E2 replacement group (E2 group), and a sham group. All rats underwent transection of the anterior cruciate ligament at the same time. After 30 days, the histological findings of knee joints by hematoxylin-eosin staining and immunofluorescence staining of protein gene product 9.5 (pan-neuronal marker), SP, and CGRP were compared among experimental groups. The degree of synovitis in the OVX group was higher than in the E2 and sham groups. No significant differences in the density of protein gene product 9.5-immunoreactive nerve fibers were observed among the three experimental groups, but the density of SP- or CGRP-immunoreactive nerve fibers in the OVX group was significantly higher than in the E2 and sham groups. These findings suggest that estrogen partly regulates intraarticular neurogenic inflammation in OA joints by modulating the expressions of neuropeptides in the synovium.

    DOI: 10.3109/03008207.2011.628059

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  • Induction of the arginine vasopressin-enhanced green fluorescent protein fusion transgene in the rat locus coeruleus

    Miwako Todoroki, Yoichi Ueta, Hiroaki Fujihara, Hiroki Otsubo, Minori Shibata, Hirofumi Hashimoto, Mizuki Kobayashi, Hirotaka Sakamoto, Mitsuhiro Kawata, Govindan Dayanithi, David Murphy, Hisanori Hiro, Ken Takahashi, Shoji Nagata

    STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS   13 ( 4 )   281 - 292   2010年7月

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    記述言語:英語   出版者・発行元:INFORMA HEALTHCARE  

    We examined the effects of intracerebroventricular (i.c.v.) administration of colchicine on the expression of the arginine vasopressin (AVP)-enhanced green fluorescent protein (eGFP) fusion gene in rats. In rats administered i.c.v. vehicle ( control), eGFP fluorescence was observed in the supraoptic nucleus ( SON), the magnocellular division of the paraventricular nucleus (PVN), the suprachiasmatic nucleus (SCN), the median eminence ( ME) and the posterior pituitary. Two days after i.c.v. administration of colchicine, eGFP fluorescence was markedly increased in the SON, the magnocellular and parvocellular divisions of the PVN, the SCN, the ME and the locus coeruleus (LC). Immunohistochemical staining for eGFP confirmed the distribution of fluorescence in both groups. In the colchicines-administered groups, immunohistochemistry for tyrosine hydroxylase (TH) revealed that the eGFP fluorescence was co-localised with TH-immunoreactivity in the LC. Similarly, in situ hybridization histochemistry for eGFP mRNA revealed a significant increase in gene expression in the LC, the SON and the PVN 12-48 h after administration of colchicine. Our results indicate that the synthesis of AVP-eGFP is upregulated in noradrenergic neurones in the LC after colchicine administration. This implies that AVP and noradrenaline, originating from LC neurones, might play a role in response to chronic stress.

    DOI: 10.3109/10253890903383406

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  • Aldosterone–sensitive NTS neurons regulate sensitivity of the baroreceptor reflex in high-sodium loaded rats

    増田他

    Journal of Pharmacological Sciences   112 ( 4 )   482 - 486   2010年4月

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  • Expression of G protein-coupled receptor 30 in the spinal somatosensory system

    Keiko Takanami, Hirotaka Sakamoto, Ken-Ichi Matsuda, Koji Hosokawa, Mayumi Nishi, Eric R. Prossnitz, Mitsuhiro Kawata

    BRAIN RESEARCH   1310   17 - 28   2010年1月

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    記述言語:英語   出版者・発行元:ELSEVIER SCIENCE BV  

    Estrogens were originally identified as the primary sex steroid hormones in females and regulators of reproductive function and sexual behavior, but it has long been suggested that estrogens also have local effects on the somatosensory system at the spinal cord level. it is well known that the effects of estrogens are mediated by nuclear estrogen receptors (ERs) through genomic action, but recently a membrane-bound G protein-coupled receptor, GPR30, was identified as a non-genomic estrogen receptor. in this study we investigated the presence and localization of GPR30 in the rat spinal cord and dorsal root ganglion (DRG) in comparison with ER alpha. Using immunohistochemistry and in situ hybridization, we showed the expression of GPR30 in DRG neurons in male and female rats at mRNA and protein levels without specific sexual difference. A dense accumulation of GPR30 immunoreactivity was observed in the outer layer of the spinal dorsal horn, and selective spinal dorsal rhizotomy revealed that GPR30 was transported from the DRG to terminals located in the spinal dorsal horn. GPR30 expression was downregulated in DRG neurons of ovariectomized female rats. The spinal somatosensory system might be modulated by estradiol via putative membrane ER, GPR30-mediated mechanism. (C) 2009 Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.brainres.2009.11.004

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  • 性機能とgastrin-releasing peptide (GRP) ニューロンシステム − EDの中枢性病態生理解明に向けて −

    坂本 浩隆, 河田光博

    自律神経   47   82 - 85   2010年

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  • Estrogen regulate itch sensation

    Keiko Takanami, Ken-ichi Matsuda, Hirotaka Sakamoto, Yukie Hirahara, Mitsuhiro Kawata

    NEUROSCIENCE RESEARCH   68   E162 - E162   2010年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2010.07.2292

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  • 超高圧電子顕微鏡を用いた脊髄gastrin-releasing peptide (GRP) 系から球海綿体脊髄核ニューロンへのシナプス入力の可視化

    坂本 浩隆

    比較内分泌学   36   146 - 148   2010年

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  • The neurobiology of psychogenic erectile dysfunction in the spinal cord

    H. Sakamoto

    Journal of Andrology   21 ( 4 )   432 - 435   2010年

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  • Characterization of In Vivo Effects of Platelet-Rich Plasma and Biodegradable Gelatin Hydrogel Microspheres on Degenerated Intervertebral Discs

    Kazuhide Sawamura, Takumi Ikeda, Masateru Nagae, Shin-ichi Okamoto, Yasuo Mikami, Hitoshi Hase, Kazuya Ikoma, Tetsuya Yamada, Hirotaka Sakamoto, Ken-ichi Matsuda, Yasuhiko Tabata, Mitsuhiro Kawata, Toshikazu Kubo

    TISSUE ENGINEERING PART A   15 ( 12 )   3719 - 3727   2009年12月

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    記述言語:英語   出版者・発行元:MARY ANN LIEBERT, INC  

    We have previously shown that administration of platelet-rich plasma-impregnated gelatin hydrogel microspheres (PRP-GHMs) into a degenerated intervertebral disc (IVD) markedly suppresses progression of IVD degeneration. In the current study, we characterized the in vivo effects of PRP-GHM treatment in a degenerated IVD model in rabbit. On magnetic resonance images, the IVD height was significantly greater after treatment with PRP-GHMs compared with phosphate-buffered saline-impregnated GHMs, PRP without GHMs, and needle puncture only. Water content was also preserved in PRP-GHM-treated IVDs. Consistent with this observation, the mRNA expression of proteoglycan core protein and type II collagen was significantly higher after PRP-GHM treatment compared with other treatment groups. No proliferating cells were found in the nucleus pulposus and inner annulus fibrosus in any groups, but the number of apoptotic cells in the nucleus pulposus after PRP-GHM treatment was significantly lower than that after other treatments. These results provide an improved understanding of the therapeutic effects of PRP-GHM treatment of degenerated IVDs.

    DOI: 10.1089/ten.tea.2008.0697

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  • Androgen Regulates the Sexually Dimorphic Gastrin-Releasing Peptide System in the Lumbar Spinal Cord that Mediates Male Sexual Function (vol 150, pg 3672, 2009)

    Hirotaka Sakamoto, Keiko Takanami, Damian G. Zuloaga, Kenichi Matsuda, Cynthia L. Jordan, S. Marc Breedlove, Mitsuhiro Kawata

    ENDOCRINOLOGY   150 ( 9 )   4461 - 4461   2009年9月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

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  • Gastrin-Releasing Peptide System in the Spinal Cord Controls Male Sexual Behaviour

    H. Sakamoto, M. Kawata

    JOURNAL OF NEUROENDOCRINOLOGY   21 ( 4 )   432 - 435   2009年4月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:WILEY-BLACKWELL PUBLISHING, INC  

    The lumbar spinal cord contains local neural circuits that are important in regulating male sexual behaviours, but the molecular mechanisms underlying these systems remain elusive. Gastrin-releasing peptide (GRP) is a member of the bombesin-like peptide family first isolated from the porcine stomach. Despite extensive pharmacological studies on the activity of bombesin-like peptides administered to mammals, little is known about the physiological functions of GRP in the spinal cord. We review recent findings on a system of neurones in the upper lumbar spinal cord, within the recently reported ejaculation generator, projecting axons containing GRP to the lower lumbar spinal cord and innervating regions known to control erection and ejaculation.

    DOI: 10.1111/j.1365-2826.2009.01847.x

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  • A high-sodium diet in streptozotocin (STZ)-induced diabetic rats impairs baroreceptor reflex; aldosterone sensitive neurons in the nucleus tractus solitarius (NTS)

    Tomoharu Masuda, Yusuke Nakamura, Masayuki Miyakawa, Yasutoshi Hirabara, Kenji Honda, Ryo Saito, Kazuhiko Arimori, Hiroyuki Nakagawa, Hirotaka Sakamoto, Mitsuhiro Kawata, Yukio Takano

    JOURNAL OF PHARMACOLOGICAL SCIENCES   109   271P - 271P   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:JAPANESE PHARMACOLOGICAL SOC  

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  • In Vivo Effects of Ovarian Steroid Hormones on the Expressions of Estrogen Receptors and the Composition of Extracellular Matrix in the Anterior Cruciate Ligament in Rats

    Atsuhiko Yoshida, Toru Morihara, Yoshiteru Kajikawa, Yuji Arai, Yasushi Oshima, Toshikazu Kubo, Ken-ichi Matsuda, Hirotaka Sakamoto, Mitsuhiro Kawata

    CONNECTIVE TISSUE RESEARCH   50 ( 2 )   121 - 131   2009年

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    記述言語:英語   出版者・発行元:TAYLOR & FRANCIS LTD  

    Female athletes have a significantly higher rate of anterior cruciate ligament (ACL) injury than their male counterparts. Sex steroid hormones are considered to have an influence as risk factors for female ACL injuries. We hypothesized that estrogen and progesterone have specific and synergistic influences on the composition of extracellular matrix in ACL. By ovariectomy (OVX) followed by subcutaneous estradiol (E2) and/or progesterone (P4) replacement, 40 female rats were divided into 5 groups: E2, P4, combined E2 and P4 (EP), OVX control, and sham group. After 30 days, using undecalcified sections of knee joints in conjunction with immunofluorescence staining of estrogen receptor and (ER and ER), collagen types 1 and 3, and cartilage oligomeric matrix protein (COMP), the immunoreactivities of these proteins in two distinct parts of ACL, proximal and middle portions, were compared semiquantitatively among experimental groups. By E2 replacement, the expressions of ER in ACL fibroblasts were elevated compared to the OVX group. At the proximal portion, the immunoreactivities of type 1 collagen by E2 replacement, type 3 collagen by P4 replacement, and COMP by E2 or P4 replacement were significantly reduced. At the middle portion, the immunoreactivity of type 3 collagen was significantly elevated by E2 replacement. However, no differences were observed between the sham and OVX groups. These findings suggest that ACL is ER-dependent and that ovarian hormones alter ligament tissue composition, especially at the proximal portion. Female hormonal influences are partly involved in the biological properties of ACL.

    DOI: 10.1080/03008200802531287

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  • Expression and its hormonal regulation of G protein-coupled receptor 30 in the rat spinal somatosensory system

    Keiko Takanami, Hirotaka Sakamoto, Ken-ichi Matsuda, Koji Hosokawa, Mayumi Nishi, Eric R. Prossnitz, Mitsuhiro Kawata

    NEUROSCIENCE RESEARCH   65   S106 - S106   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.474

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  • 新規に見出した雄の性機能を脊髄レベルで制御するgastrin-releasing peptide(GRP) ニューロンシステム

    坂本 浩隆

    比較内分泌学   35   274 - 279   2009年

  • Sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord controls masculine reproductive functions in rats

    Hirotaka Sakamoto, Ken-Ichi Matsuda, Damian G. Zuloaga, Hisayuki Hongu, Etsuko Wada, Keiji Wada, Cynthia L. Jordan, S. Marc Breedlove, Mitsuhiro Kawata

    NEUROSCIENCE RESEARCH   65   S41 - S41   2009年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

    DOI: 10.1016/j.neures.2009.09.047

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  • REGIONAL DISTRIBUTION OF importin SUBTYPE mRNA EXPRESSION IN THE NERVOUS SYSTEM: STUDY OF EARLY POSTNATAL AND ADULT MOUSE

    K. Hosokawa, M. Nishi, H. Sakamoto, Y. Tanaka, M. Kawata

    NEUROSCIENCE   157 ( 4 )   864 - 877   2008年12月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Importin-alpha and beta 1 mediate the translocation of macromolecules bearing nuclear localization signals across the nuclear pore complex. Five importin-alpha isoforms have been identified in mice and six in human. Some of these importins play an important role in neural activity such as long term potentiation, but the functional differences of each isoform in the CNS are still unclear. We performed in situ hybridization (ISH) using non-isotopic probes to clarify the expression patterns of importin-alpha subtypes (alpha 5, alpha 7, alpha 1, alpha 4, alpha 3) and importin-beta 1 in the mouse CNS of adult and early postnatal stages. The mRNAs of the importin-alpha subtypes and importin 01 were expressed throughout the CNS with specific patterns; importin-alpha 5, alpha 7, alpha 3, and beta 1 showed moderate to high expression levels throughout the brain and spinal cord; importin-alpha 4 showed a lack of expression in limited regions; and importin-alpha 1 showed a low expression level throughout the brain and spinal cord but with a moderate expression level in the olfactory bulb and reticular system. We also demonstrated that importin-alpha s and beta 1 mRNAs were predominantly expressed in neurons in the adult mouse brain by using double-labeling fluorescence ISH and immunohistochemistry. Moreover, importin-alpha s and beta 1 mRNAs were detected throughout the CNS of postnatal mice and were highly expressed in the external granule layer of the cerebellar cortex on postnatal days 0, 4, and 10. This is the first report of importin-alpha s and beta 1 expression throughout the CNS of adult mice, as well as in the developing brain, including cell type specific localization. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2008.09.045

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  • Androgen action in the brain and spinal cord for the regulation of male sexual behaviors

    Ken-ichi Matsuda, Hirotaka Sakamoto, Mitsuhiro Kawata

    CURRENT OPINION IN PHARMACOLOGY   8 ( 6 )   747 - 751   2008年12月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:ELSEVIER SCI LTD  

    Circulating levels of androgens determine the sexual differentiation of the brain and spinal cord at a critical period, Although estradiol, which is converted from testosterone by aromatase action, can explain the cytological basis for the sexual dimorphism, androgen has its own regulatory mechanism to promote male-specific behavior through receptors. The central nervous system (CNS) employs a sex-specific neuronal network involving peptides and steroids for the expression of the sexual phenotype. Elucidation of the molecular mechanism along with the neuroanatomical background should guide the development of novel pharmacotherapeutics for sexual behavior dysfunction.

    DOI: 10.1016/j.coph.2008.08.010

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  • THE SINGLE-PROLONGED STRESS PARADIGM ALTERS BOTH THE MORPHOLOGY AND STRESS RESPONSE OF MAGNOCELLULAR VASOPRESSIN NEURONS

    T. Yoshii, H. Sakamoto, M. Kawasaki, H. Ozawa, Y. Ueta, T. Onaka, K. Fukui, M. Kawata

    NEUROSCIENCE   156 ( 3 )   466 - 474   2008年10月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Vasopressin (AVP) plays an important role in anxiety-related and social behaviors. Single-prolonged stress (SPS) has been established as an animal acute severe stress model and has been shown to induce a lower adrenocorticotropic hormone (ACTH) response upon cortisol challenge. Here, we show results from immunoassays for AVP, ACTH, and corticosterone (CORT), and in situ hybridizations for AVP mRNA performed 7 days after SPS exposure. Immunofluorescence for AVP was also performed during the 7-day period following SPS exposure and after an additional forced swimming stress paradigm. We observed that the plasma concentrations of AVP, ACTH, and CORT were not altered by SPS; ACTH content in the pituitary and AVP mRNA expression in the supraoptic nucleus (SON) were significantly reduced by SPS. During the 7-day period following SPS, the intensity of immunoreactivity, the size of the soma, and the immunoreactive optical density of the dendrites of AVP neurons in the SON all increased. An apparent reduction in the intensity of AVP immunoreactivity was observed in the SON at 4 h after additional stress. Additional forced swimming led to a rapid increase in the dendritic AVP content only in the controls and not in the SPS-treated rats. These findings suggest that AVP is a potential biomarker for past exposure to severe stress and that alterations in AVP may affect the development of pathogenesis in stress-related disorders. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2008.07.049

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  • Expression and intracellular distribution of the G protein-coupled receptor 30 in rat hippocampal formation

    KenIchi Matsuda, Hirotaka Sakamoto, Hiroko Mori, Koji Hosokawa, Akeo Kawamura, Minoru Itose, Mayumi Nishi, Eric R. Prossnitz, Mitsuhiro Kawata

    NEUROSCIENCE LETTERS   441 ( 1 )   94 - 99   2008年8月

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    記述言語:英語   出版者・発行元:ELSEVIER IRELAND LTD  

    Although the expression and distribution of nuclear estrogen receptors in the hippocampus has been described, it has been proposed that the nuclear receptors may not explain all aspects of estrogen function in the hippocampus. Recently, a G protein-coupled receptor for estrogen, GPR30, was identified as a membrane-localized estrogen receptor in several cancer cell lines. In this study, we examined the expression and intracellular distribution of GPR30 in the rat hippocampal formation. We found expression of GPR30 in pyramidal cells of CA1-3 and granule cells of the dentate gyrus at both mRNA and protein levels. Specific markers for intracellular organelles and immunoelectron microscopy revealed that GPR30 was mainly localized to the Golgi apparatus and partially in the endoplasmic reticulum of the neuron but could not detect the protein at the cell surface. Expression levels were not different among male, female in proestrus and female in estrus at the adult stage, but were higher in newborn male than newborn female. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

    DOI: 10.1016/j.neulet.2008.05.108

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  • Steroid receptor signalling in the brain - Lessons learned from molecular imaging

    M. Kawata, M. Nishi, K. Matsuda, H. Sakamoto, N. Kaku, M. Masugi-Tokita, K. Fujikawa, Y. Hirahara-Wada, K. Takanarni, H. Mori

    JOURNAL OF NEUROENDOCRINOLOGY   20 ( 6 )   673 - 676   2008年6月

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    記述言語:英語   掲載種別:書評論文,書評,文献紹介等   出版者・発行元:BLACKWELL PUBLISHING  

    Studies with green fluorescent protein (GFP) have revealed the subcellular distribution of many steroid hormone receptors to be much more dynamic than previously thought. Fluorescence resonance energy transfer (FRET) and fluorescence recovery after photobleaching (FRAP) are powerful techniques with which to examine protein-protein interaction and the mobility of tagged proteins, respectively. FRET analysis revealed that steroid treatment (with corticosterone or testosterone) induces direct interaction of the glucocorticoid receptor (GR) and importin alpha in the cytoplasm and that, shortly after nuclear entry, the GR detaches from importin alpha. The mineralocorticoid receptor (MR) and androgen receptor (AR) show the same trafficking. Upon oestradiol treatment, ER alpha and ER beta in the same cell are relocalised to form a discrete pattern and are localised in the same discrete cluster (subnuclear foci). FRAP analysis showed that nuclear ER alpha and ER beta are most dynamic and mobile in the absence of the ligand, and that mobility decreases slightly after ligand treatment. Genomic as well as non-genomic actions of steroid hormones influence the cellular function of target tissues spacio-temporally.

    DOI: 10.1111/j.1365-2826.2008.01727.x

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  • Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing

    Yoshiteru Kajikawa, Toru Morihara, Hirotaka Sakamoto, Ken-Ichi Matsuda, Yasushi Oshima, Atsuhiko Yoshida, Masateru Nagae, Yuji Arai, Mitsuhiro Kawata, Toshikazu Kubo

    JOURNAL OF CELLULAR PHYSIOLOGY   215 ( 3 )   837 - 845   2008年6月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

    Circulation-derived cells play a crucial role in the healing processes of tissue. In early phases of tendon healing processes, circulation-derived cells temporarily exist in the wounded area to initiate the healing process and decrease in number with time. We assumed that a delay of time-dependent decrease in circulation-derived cells could improve the healing of tendons. In this study, we injected platelet-rich plasma (PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and compared the effects on activation of circulation-derived cells and enhancement of tendon healing with a control group (no PRP injection). To follow the circulation-derived cells, we used a green fluorescent protein (GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the numbers of GFP-positive cells and heat-shock protein (HSP47; collagen-specific molecular chaperone)-positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of circulation-derived cells for enhancement of the initial tendon healing process.

    DOI: 10.1002/jcp.21368

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  • Effects of single-prolonged stress on neurons and their afferent inputs in the amygdala

    H. Cui, H. Sakamoto, S. Higashi, M. Kawata

    NEUROSCIENCE   152 ( 3 )   703 - 712   2008年3月

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    The amygdala modulates memory consolidation with the storage of emotionally relevant information and plays a critical role in fear and anxiety. We examined changes in neuronal morphology and neurotransmitter content in the amygdala of rats exposed to a single prolonged stress (SPS) as a putative animal model for human post-traumatic stress disorder (PTSD). Rats were perfused 7 days after SPS, and intracellular injections of Lucifer Yellow were administered to neurons of the basolateral (BLA) and central amygdala (CeA) to analyze morphological changes at the cellular level. A significant increase of dendritic arborization in BLA pyramidal neurons was observed, but there was no effect on CeA neurons. Neuropeptide Y (NPY) was abundant in BLA under normal conditions. The local concentration and number of immunoreactive fibers of NPY in the BLA of SPS-exposed rats were increased compared with the control. No differences were observed in this regard in the CeA. Double immunostaining by fluorescence and electron microscopy revealed that NPY immunoreactive terminals were closely associated with calcium/calmodulin H-dependent protein kinase (CaMKII: a marker for pyramidal neurons)-positive neurons in the BLA, which were immunopositive to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). SPS had no significant effect on the expression of CaMKII and MR/GR expression in the BLA. Based on these findings, we suggest that changes in the morphology of pyramidal neurons in the BLA by SPS could be mediated through the enhancement of NPY functions, and this structural plasticity in the amygdala provides a cellular and molecular basis to understand for affective disorders. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2007.12.028

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  • Behavior of host and graft cells in the early remodeling process of rotator cuff defects in a transgenic animal model

    Yoshio Iwata, Toru Morihara, Hisakazu Tachiiri, Yoshiteru Kajikawa, Atsuhiko Yoshida, Yuji Arai, Daisaku Tokunaga, Hirotaka Sakamoto, Ken-ichi Matsuda, Masao Kurokawa, Mitsuhiro Kawata, Toshikazu Kubo

    JOURNAL OF SHOULDER AND ELBOW SURGERY   17 ( 1 )   101S - 107S   2008年1月

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    記述言語:英語   出版者・発行元:MOSBY-ELSEVIER  

    Autologous tissue graft is one of the treatment options for a large rotator cuff defect. To develop appropriate strategies for enhanced solid graft integration at the bone-tendon interface and tendon-tendon interface, clarifying the fate of the graft and host cells that contribute to repair and remodeling is necessary. We have developed a new grafting model using green fluorescent protein-transgenic rats and wild-type rats to simulate autologous transplantation for examining the behavior of the host and graft cells in the remodeling process after tendon grafting. We found that the host cells commenced proliferation in the graft at 1 day after grafting. The host cells infiltrated into the graft from the subacromial synovium, proximal tendon, and bone-tendon insertion. The number of graft-derived cells decreased with time. Our result clearly demonstrated that host cells, rather than graft cells, were essential for rotator cuff remodeling after tendon grafting for rotator cuff defect.

    DOI: 10.1016/j.jse.2007.07.008

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  • Mode of action and functional significance of estrogen-inducing dendritic growth, spinogenesis, and synaptogenesis in the developing purkinje cell

    Katsunori Sasahara, Hanako Shikimi, Shogo Haraguchi, Hirotaka Sakamoto, Shin-ichiro Honda, Nobuhiro Harada, Kazuyoshi Tsutsui

    JOURNAL OF NEUROSCIENCE   27 ( 28 )   7408 - 7417   2007年7月

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    記述言語:英語   出版者・発行元:SOC NEUROSCIENCE  

    Neurosteroids are synthesized de novo from cholesterol in the brain. To understand neurosteroid action in the brain, data on the regio- and temporal-specific synthesis of neurosteroids are needed. Recently, we identified the Purkinje cell as an active neurosteroidogenic cell. In rodents, this neuron actively produces several neurosteroids including estradiol during neonatal life, when cerebellar neuronal circuit formation occurs. Estradiol may be involved in cerebellar neuronal circuit formation through promoting neuronal growth and neuronal synaptic contact, because the Purkinje cell expresses estrogen receptor-beta (ER beta). To test this hypothesis, in this study we examined the effects of estradiol on dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell using neonatal wild-type (WT) mice or cytochrome P450 aromatase knock-out (ArKO) mice. Administration of estradiol to neonatal WT or ArKO mice increased dendritic growth, spinogenesis, and synaptogenesis in the Purkinje cell. In contrast, WT mice treated with tamoxifen, an ER antagonist, or ArKO mice exhibited decreased Purkinje dendritic growth, spinogenesis, and synaptogenesis at the same neonatal period. To elucidate the mode of action of estradiol, we further examined the expression of brain-derived neurotrophic factor ( BDNF) in response to estrogen actions in the neonate. Estrogen administration to neonatal WT or ArKO mice increased the BDNF level in the cerebellum, whereas tamoxifen decreased the BDNF level in WT mice similar to ArKO mice. BDNF administration to tamoxifen-treated WT mice increased Purkinje dendritic growth. These results indicate that estradiol induces dendritic growth, spinogenesis, and synaptogenesis in the developing Purkinje cell via BDNF action during neonatal life.

    DOI: 10.1523/JNEUROSCI.0710-07.2007

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  • GFP chimeric models exhibited a biphasic pattern of mesenchymal cell invasion in tendon healing

    Yoshiteru Kajikawa, Toru Morihara, Nobuyoshi Watanabe, Hirotaka Sakamoto, Ken-Ichi Matsuda, Masashi Kobayash, Yasushi Oshima, Atsuhiko Yoshida, Mitsuhiro Kawata, Toshikazu Kubo

    JOURNAL OF CELLULAR PHYSIOLOGY   210 ( 3 )   684 - 691   2007年3月

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    記述言語:英語   出版者・発行元:WILEY-LISS  

    The healing of an injured musculoskeletal system requires an influx of mesenchymal cells that can differentiate into osteoblasts, fibroblasts, chondroblasts, and skeletal myoblasts. However, whether these mesenchymal cells arise from the circulation (bone marrow) or the injured tissues themselves has been controversial. To reveal the spatiotemporal characteristics of the reparative mesenchymal cells, we investigated the healing process after patellar tendon injury using two types of green fluorescent protein (GFP) chimeric rats; one expressing GFP in the circulating cells, and the other expressing it in the patellar tendon. We analyzed the behavior of GFP-positive cells after experimental tendon injury in both chimeric rats to clarify the origin of reparative cells. At 24 h after the injury, the wound contained circulation-derived cells but not tendon-derived cells. Tendon-derived cells first appeared in the wounded area at 3 days after the injury, and had significantly increased in number with time and had maintained a high level of proliferative activity until 7 days after the injury, whereas the circulation-derived cells had decreased in number and had been replaced by the tendon-derived cells. These findings suggest that circulation-derived and tendon-derived cells contribute to the healing of tendons in different periods as part of a biphasic process.

    DOI: 10.1002/jcp.20876

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  • Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres

    Masateru Nagae, Takumi Ikeda, Yasuo Mikami, Hitoshi Hase, Hitoshi Ozawa, Ken-Ichi Matsuda, Hirotaka Sakamot, Yasuhiko Tabata, Mitsuhiro Kawata, Toshikazu Kubo

    TISSUE ENGINEERING   13 ( 1 )   147 - 158   2007年1月

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    記述言語:英語   出版者・発行元:MARY ANN LIEBERT INC  

    This study evaluated the regenerative effects of platelet-rich plasma (PRP) for the degenerated intervertebral disc (IVD) in vivo. After induction of IVD degeneration in rabbits, we prepared PRP by centrifuging blood obtained from these rabbits. These PRP were injected into the nucleus pulposus (NP) of the degenerated IVDs after impregnation into gelatin hydrogel microspheres that can immobilize PRP growth factors physiochemically and release them in a sustained manner with the degradation of the microspheres. As controls, microspheres impregnated with phosphate-buffered saline (PBS) and PRP without microspheres were similarly injected. Histologically, notable progress in IVD degeneration with time courses was observed in the PBS control, PRP-only, and sham groups. In contrast, progress was remarkably suppressed over the 8-week period in the PRP group. Moreover, in immunohistochemistry, intense immunostaining for proteoglycan in the NP and inner layer of the annulus fibrosus was observed 8 weeks after administration of PRP-impregnated microspheres. Almost all microspheres were indistinct 8 weeks after the injection, and there were no apparent side effects in this study. Our results suggest that the combined administration of PRP and gelatin hydrogel microspheres into the IVD may be a promising therapeutic modality for IVD degeneration.

    DOI: 10.1089/ten.2006.0042

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  • 内分泌学的PTSDストレスモデルはバソプレッシン系にも影響する

    吉井 崇喜, 坂本 浩隆, 川崎 展, 小澤 一史, 尾仲 達史, 上田 陽一, 福居 顯二, 河田 光博

    日本内分泌学会雑誌   82 ( 2 )   368 - 368   2006年9月

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    記述言語:日本語   出版者・発行元:(一社)日本内分泌学会  

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  • The vasopressin dynamism is altered by PTSD model stress

    Takanobu Yoshii, Hirotaka Sakamoto, Makoto Kawasaki, Hitoshi Ozawa, Yoichi Ueta, Kenji Fukui, Mitsuhiro Kawata

    FRONTIERS IN NEUROENDOCRINOLOGY   27 ( 1 )   46 - 46   2006年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.yfrne.2006.03.094

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  • Distribution of gastrin releasing peptide in the rat lumbar spinal cord is sexually dimorphic and regulated by androgen

    Hirotaka Sakamoto, Mitsuhiro Kawata

    FRONTIERS IN NEUROENDOCRINOLOGY   27 ( 1 )   146 - 146   2006年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    DOI: 10.1016/j.yfrne.2006.03.254

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  • Intrauterine proximity to male fetuses affects the morphology of the sexually dimorphic nucleus of the preoptic area in the adult rat brain

    M Pei, K Matsuda, H Sakamoto, M Kawata

    EUROPEAN JOURNAL OF NEUROSCIENCE   23 ( 5 )   1234 - 1240   2006年3月

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    記述言語:英語   出版者・発行元:BLACKWELL PUBLISHING  

    Previous studies on polytocous rodents have revealed that the fetal intrauterine position influences its later anatomy, physiology, reproductive performance and behavior. To investigate whether the position of a fetus in the uterus modifies the development of the brain, we examined whether the structure of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of rat brains accorded to their intrauterine positions. Brain sections of adult rats gestated between two male fetuses (2M) and between two female fetuses (2F) in the uterus were analysed for their immunoreactivity to calbindin-D28k, which is a marker of the SDN-POA. The SDN-POA volume of the 2M adult males was greater than that of the 2F adult males, whereas the SDN-POA volume of the 2M and 2F adult females showed no significant difference. This result indicated that contiguous male fetuses have a masculinizing effect on the SDN-POA volume of the male. To further examine whether the increment of SDN-POA volume in adulthood was due to exposure to elevated steroid hormones during fetal life, concentrations of testosterone and 17 beta-estradiol in the brain were measured with 2M and 2F fetuses during gestation, respectively. On gestation day 21, the concentrations of testosterone and 17 beta-estradiol in the brain were significantly higher in the 2M male rats as compared with the 2F male rats. The results suggested that there was a relationship between the fetal intrauterine position, hormone transfer from adjacent fetuses and the SDN-POA volume in adult rat brains.

    DOI: 10.1111/j.1460-9568.2006.04661.x

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  • Effects of single-prolonged stress on dendritic arborization of neurons in the central and basolateral amygdala

    Honghai Cui, Hirotaka Sakamoto, Mitsuhiro Kawata

    NEUROSCIENCE RESEARCH   55   S180 - S180   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • 多血小板血漿含浸ゼラチンハイドロゲル粒子の椎間板内投与による椎間板再生効果の組織学的検討 査読

    長江将輝, 池田巧, 三上靖夫, 長谷斉, 小澤一史, 松田賢一, 坂本浩隆, 田畑泰彦, 久保俊一, 河田光博

    第111 回日本解剖学会総会・全国学術集会(2006.3.29-31. 相模原)   2006年

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    記述言語:日本語  

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  • PTSD model stress changes the vasopressin dynamism

    Yoshii Takanobu, Hirotaka Sakamoto, Makoto Kawasaki, Hitoshi Ozawa, Yoichi Ueta, Kenji Fukui, Mitsuhiro Kawata

    NEUROSCIENCE RESEARCH   55   S91 - S91   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • 発達期の小脳プルキンエ細胞における25-Dxの発現 ― プルキンエ細胞が合成するプロゲステロンの作用機構 ―

    筒井和義ら, 番目

    生体の科学   56:296–302   2006年

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  • Dendritic growth, spinogenesis and synaptogenesis in response to neurosteroids in the developing Purkinje cell

    Kazuyoshi Tsutsui, Hirotaka Sakamoto, Katsunori Sasahara, Hanako Shikimi, Kazuyoshi Ukena, Mitsuhiro Kawata

    NEUROSCIENCE RESEARCH   55   S27 - S27   2006年

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER IRELAND LTD  

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  • IIA-21 GFP骨髄キメラを用いた腱修復における未分化間葉系細胞の起源の解析(技術,一般演題発表,第46回日本組織細胞化学会総会・学術集会)

    梶川 佳照, 坂本 浩隆, 松田 賢一, 渡邉 信佳, 大島 康史, 吉田 敦彦, 久保 俊一, 河田 光博

    日本組織細胞化学会総会プログラムおよび抄録集   ( 46 )   2005年

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    記述言語:日本語   出版者・発行元:日本組織細胞化学会  

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  • Expression and localization of 25-Dx, a membrane-associated putative progesterone-binding protein, in the developing Purkinje cell

    H Sakamoto, K Ukena, H Takemori, M Okamoto, M Kawata, K Tsutsui

    NEUROSCIENCE   126 ( 2 )   325 - 334   2004年

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    記述言語:英語   出版者・発行元:PERGAMON-ELSEVIER SCIENCE LTD  

    Neurosteroids are synthesized de novo in the brain and the cerebellar Purkinje cell is a major site for neurosteroid formation. We have demonstrated that the rat Purkinje cell actively produces progesterone de novo from cholesterol only during neonatal life and progesterone promotes dendritic growth, spinogenesis and synaptogenesis via its nuclear receptor in this neuron. On the other hand, 25-Dx, a putative membrane progesterone receptor, has been identified in the rat liver. In this study, we therefore investigated the expression and localization of 25-Dx in the Purkinje cell to understand the mode of progesterone actions in this neuron. Reverse transcription-PCR and Western immunoblot analyses revealed the expressions of 25-Dx mRNA and 25-Dx-like protein in the rat cerebellum, which increased during neonatal life. By immunocytochemistry, the expression of 25-Dx-like protein was localized in the Purkinje cell and external granule cell layer. At the ultrastructural level, we further found that 25-Dx-like immunoreactivity was associated with membrane structures of the endoplasmic reticulum and Golgi apparatus in the Purkinje cell. These results indicate that the Purkinje cell expresses the putative membrane progesterone receptor, 25-Dx during neonatal life. Progesterone may promote dendritic growth, spinogenesis and synaptogenesis via 25-Dx as well as its nuclear receptor in the Purkinje cell in the neonate. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

    DOI: 10.1016/j.neuroscience.2004.04.003

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  • Neonatal expression of progesterone receptor isoforms in the cerebellar Purkinje cell in rats

    H Sakamoto, H Shikimi, K Ukena, K Tsutsui

    NEUROSCIENCE LETTERS   343 ( 3 )   163 - 166   2003年6月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation. Progesterone synthesized de novo in developing PCs participates in the promotion of dendritic growth, spinogenesis and synaptogenesis in this neuron and such organizing actions may contribute to the formation of the cerebellar neuronal circuit during rat neonatal life. Progesterone receptors (PR) occur as two isoforms (PR-A and PR-B) derived from a single gene. To clarify the mode of organizing actions of progesterone, therefore, we examined the expression of these PR isoforms in the rat cerebellum during development. Western immunoblot analysis revealed that both PR isoforms were expressed highly in the cerebellum during neonatal life and the expression decreased thereafter. PR-like immunoreactivity was localized primarily in PCs in the neonatal cerebellum. Thus, progesterone may act directly on PCs via PR isoforms to promote its dendritic growth, spinogenesis and synaptogenesis. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-9340(03)000362-8

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  • エストロゲンが誘導する小脳プルキンエ細胞の発達:アロマターゼノックアウトによる解析

    食見花子, 坂本浩隆, 浮穴和義, 原田信広, 筒井和義

    日本比較内分泌学会大会及びシンポジウムプログラム・講演要旨   28th   25   2003年

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    記述言語:日本語  

    J-GLOBAL

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  • Dendritic spine formation in response to progesterone synthesized de novo in the developing Purkinje cell in rats

    Hirotaka Sakamoto, Kazuyoshi Ukena, Kazuyoshi Tsutsui

    Neuroscience Letters   322 ( 2 )   111 - 115   2002年4月

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    記述言語:英語   出版者・発行元:Elsevier Ireland Ltd  

    The cerebellar Purkinje cell (PC) is a typical site for neurosteroid formation. We have demonstrated that this neuron possesses intranuclear receptor for progesterone and actively synthesizes progesterone de novo from cholesterol only during rat neonatal life, when the formation of the cerebellar cortex occurs dramatically. In this study, we therefore analyzed the effect of progesterone on dendritic spine formation of the PC. In vitro studies using cerebellar slice cultures from newborn rats showed that progesterone increases the density of PC dendritic spines in a dose-dependent manner. This effect was blocked by the progesterone receptor antagonist, RU486. Furthermore, trilostane, a specific inhibitor of progesterone synthesis, inhibited the increase of spine density. These results suggest that progesterone can promote dendritic spine formation, and endogenous progesterone synthesized de novo in the developing PC may induce such an effect. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(02)00077-0

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  • Effects of progesterone synthesized de novo in the developing Purkinje cell on its dendritic growth and synaptogenesis

    坂本浩隆他

    J. Neurosci.   21:6221-6232   2001年

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  • Activity and localization of 3β-hydroxysteroid dehydrogenase/Δ5-Δ4-isomerase in the zebrafish central nervous system

    坂本浩隆他

    J. Comp. Neurol.   439:291-305.   2001年

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  • Existence of galanin in lumbosacral sympathetic ganglionic neurons that project to the quail uterine oviduct

    H Sakamoto, T Ubuka, C Kohchi, D Li, K Ukena, K Tsutsui

    ENDOCRINOLOGY   141 ( 12 )   4402 - 4412   2000年12月

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    記述言語:英語   出版者・発行元:ENDOCRINE SOC  

    Oviposition in birds is conducted by vigorous contractions of the uterine oviduct. We recently isolated an oviposition-inducing peptide that was identified as avian galanin from mature quail oviducts. This peptide was localized in neuronal fibers terminating in muscle layers in the uterine oviduct and evoked vigorous uterine contractions through binding to receptors located in the uterus. However, no cell bodies that express avian galanin were detected in the uterus or other oviduct regions. To understand the control mechanism of avian oviposition by galanin, me identified the neurons that synthesize galanin and project to the uterus with the combination of retrograde labeling with neurobiotin and immunocytochemistry for galanin in mature Japanese quails. Retrograde labeling with neurobiotin from the uterus revealed that lumbosacral sympathetic ganglionic neurons located in the uterine side projected their axons to the uterine muscle layer. Abundant elementary granules were observed in somata of the retrogradely labeled sympathetic ganglionic neurons, suggesting that labeled neurons may function as a neurosecretory cell. Immunocytochemical analysis with the antiserum against avian galanin showed an intense immunoreaction restricted to somata of the retrograde-labeled ganglionic neurons. Preabsorbing the antiserum with avian galanin resulted in a complete absence of the immunoreaction. Competitive enzyme-linked immunosorbent assay using antigalanin serum confirmed that avian galanin existed in the sympathetic ganglionic neurons. Expression of the avian galanin messenger RNA in the neurons was further verified by Northern blot analysis. In addition, both avian galanin and its messenger RNA in the neurons were highly expressed in mature birds, unlike in immature birds.
    These results suggest that lumbosacral sympathetic ganglionic neurons innervating the uterine muscle produce avian galanin in mature birds. Because this peptide acts directly on the uterus to evoke oviposition through a mechanism of the induction of vigorous uterine contraction, galaninergic innervation of the uterine oviduct may be essential for avian oviposition.

    DOI: 10.1210/en.141.12.4402

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  • Development of the myotomal neuromuscular system in embryonic and larval angelfish, Pterophyllum scalare

    H Sakamoto, M Yoshida, T Sakamoto, K Uematsu

    ZOOLOGICAL SCIENCE   16 ( 5 )   775 - 784   1999年10月

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    記述言語:英語   出版者・発行元:ZOOLOGICAL SOC JAPAN  

    To reveal the developmental sequence of the myotomal neuromuscular system in a teleost angelfish, Pterophyllum scalare, we investigated the differentiation and axonal outgrowth of the somatic spinal motoneurons as well as the differentiation of the axial muscles by means of anatomical and histochemical methods. Acetylcholinesterase histochemistry and retrograde labeling with HRP revealed two large motoneurons in each spinal hemisegment in the late embryos. To clarify the posthatching change of the motoneuron number, the number of axons in the anal-level ventral root was counted, since ChAT-immunohistochemical labeling of cholinergic spinal neurons and electron microscopic observation in the adult showed that the ventral roots around the anal level contained only somatic motor axons. We found that 15 primary motoneurons in each spinal hemisegment participated in the muscle innervation in just-hatched larvae. The motor axons rapidly increased in number beyond the adult level within three days posthatching, and then decreased to reach the adult level within a few weeks. The result suggests that competition among the motoneurons for their target muscles takes place. To reveal the temporal sequence of differentiation of the myotomal muscle fibers, in addition to electron microscopic observation of the muscle, a fluorescent mitochondrial marker dimethylaminostyrylethylpyridiniumiodine (DASPEI) was used to detect red muscle fibers. In the late embryo, immature white muscle fibers subserving the twitching movement of the animal in the egg capsule were observed. Differentiation of the red muscle was not evident until day 10. The present results show that a complete set of the axial muscle motoneurons differentiates before the differentiation of the multiple muscle fiber types in the angelfish.

    DOI: 10.2108/zsj.16.775

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  • Naturally occurring somatic motoneuron death in a teleost angelfish, Pterophyllum scalare

    H Sakamoto, M Yoshida, K Uematsu

    NEUROSCIENCE LETTERS   267 ( 2 )   145 - 148   1999年5月

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    記述言語:英語   出版者・発行元:ELSEVIER SCI IRELAND LTD  

    Naturally occurring somatic motoneuron death in a teleost angelfish, Pterophyllum scalare, was investigated histochemically and electron microscopically. The number of motor axons in the ventral root, which corresponds to the motoneuron number in spinal hemisegment, was rapidly increased beyond the adult value within 3 days after hatching, and then decreased to reach the adult value within a few weeks. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) histochemistry, which detects fragmented nuclear DNA characteristic to apoptotic cells, showed that the apoptotic cells are located in the motor column of the cord in the larvae at specific developmental stages. Electron microscopic observations of the spinal cells further confirmed the motoneuron apoptosis. The present data suggest that the massive death of somatic motoneurons at certain ontogenic stages which has been known to occur in higher vertebrates also takes place in fish. (C) 1999 Elsevier Science ireland Ltd. All rights reserved.

    DOI: 10.1016/S0304-3940(99)00353-5

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▼全件表示

講演・口頭発表等

  • 霊長類ニホンザルにおけるGastrin-releasing peptide神経系の機能局在

    第123回日本解剖学会総会・学術集会  2018年 

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  • 雄の性機能を司る脳–脊髄神経ネットワーク 〜神経ペプチド回路系に着目して

    第123回日本解剖学会総会・学術集会  2018年 

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  • コペプチンからバソプレシン遺伝子の転写-翻訳-プロセシングを解析する試み

    第44回日本神経内分泌学会学術集会  2017年 

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  • Oxytocinergic projections facilitate male sexual behavior via the spinal gastrin-releasing peptide system

    26th International Behavioral Neuroscience Society  2017年 

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  • 神経ペプチド系の起源:原始左右相称動物扁形動物ヒラムシのバソプレシン・神経ペプチドY

    第27回日本行動神経内分泌研究会  2017年 

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  • Morphological and molecular evolutional analyses of itch focused on the gastrin-releasing peptide system in mammals

    9th World congress of itch  2017年 

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  • ホルモンによる知覚調節への影響

    第27回日本行動神経内分泌研究会  2017年 

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  • 先端的遺伝子改変ラットを用いてオキシトシン受容体の中枢機能を解析する試み

    日本動物学会第88回大会  2017年 

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    日本アンドロロジー学会第36回学術大会  2017年 

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  • Morphological and molecular evolutional analyses of itch focused on the gastrin-releasing peptide system in mammals

    9th World congress of itch  2017年 

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  • 原始左右相称動物・扁形動物ヒラムシにおける神経内分泌系:バソプレシンと神経ペプチドY

    日本動物学会第88回大会  2017年 

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  • オキシトシン受容体の中枢機能解明を目指した先端的遺伝子改変ラットの作出

    生物系三学会中国四国支部大会(第69回動物学会中国四国支部会)  2017年 

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  • 慢性ストレスは男性の性機能障害とかゆみ感覚の過敏を引き起こす

    生物系三学会中国四国支部大会(第69回動物学会中国四国支部会)  2017年 

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  • Oxytocinergic projections facilitate male sexual behavior via the spinal gastrin-releasing peptide system

    26th International Behavioral Neuroscience Society  2017年 

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  • 原始左右相称動物・扁形動物ヒラムシにおけるバソプレシン・神経ペプチドYの起源

    生物系三学会中国四国支部大会(第69回動物学会中国四国支部会)  2017年 

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  • 遺伝子改変ラットを用いてオキシトシン受容体ニューロンを解析する試み

    第27回日本行動神経内分泌研究会  2017年 

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  • 慢性ストレスによる雄の性機能と痒み感覚への影響の解析

    第27回日本行動神経内分泌研究会  2017年 

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  • 神経解剖学を通したラット研究の新たな展開

    遺伝研 研究会 マウスとラットで拓く新しい比較実験動物学  2017年 

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  • オキシトシン受容体-関連遺伝子改変ラットを用いた性行動調節に関わる神経回路系の解析

    第44回日本神経内分泌学会学術集会  2017年 

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  • ラットにおける神経ペプチドホルモンの放出動態を組織化学的に捉える試み

    第57回日本組織細胞化学会総会・学術集会  2016年 

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  • 卒後・生涯教育プログラム 基礎系:「オキシトシンと性機能」

    日本性機能学会第27回学術総会 第26回日本性機能学会中部総会 11th Japan-ASEAN Conference on Men’s Health & Aging  2016年 

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  • 分子・神経内分泌動態の組織細胞化学的可視化

    第57回日本組織細胞化学会総会・学術集会  2016年 

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  • ニホンザル脊髄における痒み特異的伝達分子gastrin-releasing peptide受容体の発現

    第57回日本組織細胞化学会総会・学術集会  2016年 

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  • Expression of gastrin-releasing peptide in the trigeminal sensory system in the musk shrew, Suncus murinus

    2016年 

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  • 食虫類スンクス三叉神経知覚系におけるgastrin-releasing peptideの発現

    第39回日本神経科学大会  2016年 

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  • ラット視床下部–下垂体系におけるCD38の発現と細胞内局在

    第39回日本神経科学大会  2016年 

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  • Expression and subcellular localization of CD38 in the hypothalamo-neurohypophysial system in rats

    2016年 

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  • オキシトシンによるシナプスを介さない雄の性機能制御機構

    第43回日本神経内分泌学会  2016年 

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  • GnRH-like peptide in the platyhelminth (flatworm, Stylochoplana pusilla): A possible evolutional origin

    第22回国際動物学会 第87回日本動物学会 合同大会  2016年 

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    第43回日本神経内分泌学会  2016年 

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  • 雄の性機能を司る脊髄神経回路系の機能解析:Grp-promoter-Venusトランスジェニックラットの作出と利用

    第43回日本神経内分泌学会  2016年 

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  • 免疫電子顕微鏡法による痒みの神経回路網解析

    日本解剖学会第71回中国・四国学術集会  2016年 

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    第43回日本神経内分泌学会  2016年 

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    第25回日本行動神経内分泌研究会  2016年 

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  • ガストリン放出ペプチド受容体を中心とした雄の性行動を司る脳−脊髄神経ネットワークの解析

    第25回日本行動神経内分泌研究会  2016年 

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  • 医学・生物学分野における超高圧電子顕微鏡・トモグラフィー法の再考: A revisiting study for 3D-EM

    第56回日本組織細胞化学会総会・学術集会  2015年 

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  • Effective ultrastructure neuroimaging of itch

    8th World Congress of Itch  2015年 

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  • 霊長類ニホンザルの脊髄におけるgastrin-releasing peptide系の存在

    第56回日本組織細胞化学会総会・学術集会  2015年 

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  • 哺乳類三叉神経知覚系の比較組織学的解析

    第56回日本組織細胞化学会総会・学術集会  2015年 

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  • ガストリン放出ペプチド受容体に着目した雄の性行動を司る脳−脊髄神経ネットワークの解析

    第23回日本行動神経内分泌研究会  2015年 

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    第42回日本神経内分泌学会  2015年 

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  • オキシトシンによる雄の性機能制御メカニズムの行動レベルでの解析

    第42回日本神経内分泌学会  2015年 

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  • メダカ脳・生殖腺におけるアンドロゲン受容体α/βそれぞれの発現と分布

    第86回日本動物学会  2015年 

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  • ‘Volume transmission’ role for oxytocin projections in the lumbar spinal cord controlling male sexual function

    Parvo- and Magnocellular Symposium Sendai (PMSS)  2015年 

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  • 魚類および両生類・神経系におけるガストリン放出ペプチド系の同定

    第86回日本動物学会  2015年 

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  • 原始左右相称動物・扁形動物ヒラムシにおけるGnRHの同定

    第86回日本動物学会  2015年 

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  • 三次元電顕法を用いて開口分泌を捉える試み

    SSSEM研究部会&生理研研究会 合同ワークショップ 「電子顕微鏡ビッグデータが拓くバイオメディカルサイエンス」 ~電子顕微鏡による生物構造情報の抽出~  2015年 

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  • AVP-eGFP TgラットにおけるインビボGFP動態

    第56回日本組織細胞化学会総会・学術集会  2015年 

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  • 神経ペプチド・ホルモン分子の進化と機能 行動制御モデルとしてのスンクス

    第4回日本実験動物科学シンポジウム 新たな疾患モデル動物が切り開く橋渡し研究  2015年 

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  • Generation and characterization of a transgenic rat line expressing Venus under control of the gastrin-releasing peptide promoter

    第120回日本解剖学会総会・全国学術集会/第92回日本生理学会大会 合同大会  2015年 

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  • GRPRを標的としたトランスジェニックラットの作出と特徴づけ

    日本動物学会中国四国支部 第67 回大会講演要旨  2015年 

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  • ネッタイツメガエルにおけるガストリン放出ペプチド系の存在と機能

    日本動物学会中国四国支部 第67 回大会講演要旨  2015年 

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  • GRPプロモータ制御下にVenusを発現するトランスジェニックラットを用いた脊髄GRPニューロン系の解析

    第38回日本神経科学大会  2015年 

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  • 男性性機能を制御する神経ネットワークと神経ホルモンとの機能連関

    第25回日本性機能学会中部総会  2015年 

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  • ガストリン放出ペプチド・プロモータ制御下でVenusを発現するトランスジェニックラットの作出とその機能解析

    日本動物学会中国四国支部 第67 回大会講演要旨  2015年 

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  • Application of immunohistochemistry to SBF-SEM –structural analysis of itch-mediating synapse-

    第3回SEM研究会  2015年 

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  • GRPプロモータ制御下でVenusを発現するトランスジェニックラットの作出と特徴づけ

    第22回日本行動神経内分泌研究会  2015年 

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  • Oxytocin projections regulate the spinal gastrin-releasing peptide system that controls male sexual function

    第120回日本解剖学会総会・全国学術集会/第92回日本生理学会大会 合同大会  2015年 

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  • Visualization of GRP-Containing Neurons Expressing Venus Fluorescence under the Control of the GRP Promoter: A New Rodent Model for the Analyses of the Male Sexual Function and Itch Sensation at the Spinal Cord Level

    2015年 

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  • GFPは分泌性タンパク質か?AVP-GFP Tgラットを用いた解析

    第22回日本行動神経内分泌研究会  2015年 

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  • 医学生物学分野におけるHVEM・トモグラフィー法の再考

    次世代の生物電顕を考える  2014年 

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  • 雄の性機能を制御する脊髄GRP系は哺乳類に普遍的か?

    日本行動神経内分泌研究会第4回関西支部勉強会  2014年 

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  • 男性性機能と神経ホルモン

    第40回京阪泌尿器腫瘍セミナー  2014年 

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  • 免疫組織化学法を用いた体性感覚ニューロン系の3次元微細構造解析

    第55回日本組織細胞化学会総会・学術集会  2014年 

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  • 免疫電顕から探る機能神経解剖の解析法

    第55回日本組織細胞化学会総会・学術集会  2014年 

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  • Neural Circuit of the Itch to Consider From the Expression of Gastrin-Releasing Peptide in the Rat Somatosensory Systems

    第18回国際解剖学会議  2014年 

     詳細を見る

  • 箒虫動物と紐形動物のゲノム解読

    第85回日本動物学会  2014年 

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  • ラット三叉神経節および脊髄後根神経節におけるgastrin-releasing peptideの発現と回路

    第119回日本解剖学会総会・全国学術集会  2014年 

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  • Visualization of a three-dimensional ultrastructure of neuropeptide in the axon terminals by 3view-scanning electron microscopy

    第8回国際神経内分泌学会議  2014年 

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  • 雄の性行動時に脊髄で放出されるオキシトシンは脊髄gastrin-releasing peptide系を活性化する

    第119回日本解剖学会総会・全国学術集会  2014年 

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  • 脊髄に存在する雄優位の性的二型核: gastrin-releasing peptide系の性差構築メカニズム

    第119回日本解剖学会総会・全国学術集会  2014年 

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  • OXTは雄の性行動時に脊髄GRPニューロンにおけるpERK発現を誘起する

    日本行動神経内分泌研究会第4回関西支部勉強会  2014年 

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  • 感覚ニューロンにおける神経内分泌機構への形態科学的アプローチ

    日本行動神経内分泌研究会第4回関西支部勉強会  2014年 

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  • かゆみを伝える神経ネットワーク

    第41回日本神経内分泌学会  2014年 

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  • 3D electron microscopic analysis of neural network in the spinal dorsal horn

    The 24rd International Symposium of Itch  2014年 

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  • 連続ブロック表面走査型電子顕微鏡による痒み伝達感覚ニューロンの形態解析

    次世代の生物電顕を考える  2014年 

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  • Hypothalamic oxytocinergic projections mediate the spinal gastrin-releasing peptide system controlling male sexual function

    第10回国際下垂体後葉ホルモン会議  2013年 

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  • かゆみはどのように伝達するのか?

    第19回日本行動神経内分泌研究会  2013年 

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  • Oxytocinergic projections mediate the spinal gastrin-releasing peptide system controlling male sexual function

    第10回国際下垂体後葉ホルモン会議  2013年 

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  • バソプレシン-eGFPトランスジェニックラットにおけるeGFP分子の動態解析

    日本動物学会中国四国支部 第65 回大会講演要旨  2013年 

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  • 三叉神経感覚系におけるガストリン放出ペプチドの分布

    第36回日本神経科学大会 (Neuro 2013)  2013年 

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  • 超高圧電子顕微鏡を用いたラット脊髄gastrin-releasing peptide系を中心とした脊髄内局所神経回路の三次元的解析

    第118回日本解剖学会総会・全国学術集会  2013年 

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  • 三叉神経におけるガストリン放出ペプチドの発現解析

    第118回日本解剖学会総会・全国学術集会  2013年 

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  • かゆみの伝達に関わる一次感覚神経の組織学解析

    日本行動神経内分泌研究会 第3回関西支部勉強会  2013年 

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  • ラットにおける新規摂食調節関連ペプチド産生細胞の電子顕微鏡観察と絶食処理による形態学的変化

    日本行動神経内分泌研究会 第3回関西支部勉強会  2013年 

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  • Distribution of gastrin-releasing peptide in the trigeminal sensory system

    Neuro 2013  2013年 

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  • 脳のERβを標識する試み

    日本行動神経内分泌研究会 第3回関西支部勉強会  2013年 

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  • 免疫組織化学の超高圧電子顕微鏡観察への応用

    「電子顕微鏡機能イメージングの医学・生物学への応用」 〜分子から細胞までの機能イメージング〜  2013年 

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  • 雄の性行動時にオキシトシンは脊髄gastrin-releasing peptideニューロンを活性化する

    日本解剖学会第68回中国・四国学術集会  2013年 

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  • 雄の性行動は脊髄GRPニューロンにおけるpERK発現を誘起する

    第40回日本神経内分泌学会  2013年 

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  • ラットにおける視床下部新規神経ペプチドの電子顕微鏡観察

    第84回日本動物学会  2013年 

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  • マウスにおける雄の性機能を制御する脊髄gastrin-releasing peptide系の解析

    日本解剖学会第68回中国・四国学術集会  2013年 

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  • (日本版)全動物門のゲノム解読にむけて1:総論

    第84回日本動物学会  2013年 

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  • (日本版)全動物門のゲノム解読にむけて3:箒虫動物#IP. australis #IRのゲノム解読

    第84回日本動物学会  2013年 

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  • 弱毒化狂犬病ウイルストレーサーを用いた球海綿体筋から脊髄gastrin-releasing peptideニューロンへの投射解析

    第117回日本解剖学会総会・全国学術集会  2012年 

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  • ラットの視床下部新規神経ペプチドの形態学的解析-既知の生理活性物質との相関と絶 食処理に伴う変化-

    第37回日本比較内分泌学会大会  2012年 

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  • ラット感覚神経系における痒み関連分子ガストリン放出ペプチドの局在

    第39回日本神経内分泌学会  2012年 

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  • Regulation of male sexual functions by oxytocin-mediated volume transmission in the lumbar spinal cord

    第3回国際神経ペプチド学会日本支部シンポジウム  2012年 

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  • オキシトシンは腰髄gastrin-releasing peptide系を介して雄の性機能を調節する

    第39回日本神経内分泌学会  2012年 

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  • バソプレシン-eGFPトランスジェニックラットを用いた下垂体後葉における放出活性

    第39回日本神経内分泌学会  2012年 

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  • バソプレシン-eGFPトランスジェニックラットを用いた脳下垂体神経葉における放出活性

    第83回日本動物学会  2012年 

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  • 本能行動を制御する作用機序に関する神経内分泌学的研究

    第83回日本動物学会  2012年 

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  • 痒覚調節に関わる性ホルモンの作用:掻破行動解析

    第17回日本行動神経内分泌研究会  2012年 

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  • 間脳オキシトシン投射は脊髄ガストリン放出ペプチド系を介して雄の性機能を調節する

    第83回日本動物学会  2012年 

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  • バソプレシン/オキシトシンと蛍光タンパク質との融合タンパク質を発現する遺伝子改変ラットを用いた蛍光イメージング解析に関する予備的解析

    第17回日本行動神経内分泌研究会  2012年 

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  • オキシトシンニューロンの脊髄gastrin-releasing peptideニューロン系を介した雄性性機能への関与

    日本行動神経内分泌研究会 第2回関西支部勉強会  2012年 

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  • Regulation of male sexual functions by oxytocin-mediated volume transmission in the spinal cord

    US-Japan Joint Summer Program: Pauley Program  2012年 

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  • OXTニューロンは腰髄gastrin-releasing peptide系を介して雄の性機能を調節する

    第17回日本行動神経内分泌研究会  2012年 

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  • 性機能を司る脳—脊髄神経回路における非シナプス的動作メカニズム

    第35回埼玉大学脳科学セミナー  2012年 

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  • 雄の性機能を制御する脊髄ガストリン放出ペプチド系と間脳オキシトシン系との機能連関

    日本動物学会中国四国支部 第64 回大会講演要旨  2012年 

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  • 扁形動物ヒラムシにおける脳下垂体神経葉ホルモン様ペプチドを同定する試み

    第36回日本比較内分泌学会大会  2011年 

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  • トビハゼの行動制御における脳下垂体神経葉ホルモン(バソトシン・イソトシン)の役割

    第36回日本比較内分泌学会大会  2011年 

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  • メダカ脳におけるアンドロゲン受容体の発現と局在

    日本動物学会第82回旭川大会  2011年 

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  • トビハゼ(#IPeriophthalmus modestus#IR)における攻撃行動と神経葉ホルモン発現との関係

    日本動物学会第82回旭川大会  2011年 

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  • 超高圧電子顕微鏡による脊髄gastrin-releasing peptideシステムから球海綿体脊髄核への求心性入力の可視化

    第37回日本神経内分泌学会学術集会  2010年 

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  • Estrogens regulate itch sensation

    2010年 

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  • 雄の性機能を脊髄レベルで制御する神経ホルモン

    日本動物学会第81回東京大会  2010年 

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  • トビハゼの水陸両生におけるバソトシン(VT)とイソトシン(IT)の役割

    日本動物学会第81回東京大会  2010年 

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  • エストロゲンによる痒感調節

    第33回日本神経科学大会 (Neuro 2010)  2010年 

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  • 雄の性機能を制御する脊髄内神経回路

    第13回日本行動神経内分泌研究会  2010年 

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  • 平成21年度日本解剖学会奨励賞受賞者講演

    第115回日本解剖学会総会・全国学術集会  2010年 

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  • The gastrin-releasing peptide system in the lumbar spinal cord is sexually dimorphic and controls male reproductive functions in rats

    第7回国際神経内分泌会議  2010年 

     詳細を見る

  • 医学生物分野における超高圧電子顕微鏡の応用: 免疫組織化学染色法と逆行性標識法の適用例

    生理学研究所研究会23「医学生物学用超高圧電子顕微鏡(H-1250M)の30年」  2010年 

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  • 超高圧電子顕微鏡を用いた脊髄ガストリン放出ペプチド系から球海綿体脊髄核ニューロンへのシナプス入力の可視化

    第115回日本解剖学会総会・全国学術集会  2010年 

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  • 新規に見出した雄の性機能を脊髄レベルで制御するgastrin-releasing peptide(GRP)ニューロンシステム

    第340回岡山大学生物科学セミナー  2009年 

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  • Direct synaptic inputs from a gastrin-releasing peptide system to neurons of the spinal nucleus of bulbocavernosus revealed by the HVEM

    第50回日本組織細胞化学会  2009年 

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  • 脊髄レベルで雄の性機能を制御する gastrin-releasing peptide (GRP) ニューロンシステム

    日本解剖学会第64回中国・四国学術集会  2009年 

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  • 雄の性機能を制御するラット腰髄ガストリン放出ペプチド系におけるストレス応答:心因性勃起障害治療への新たな展望

    第36回日本神経内分泌学会  2009年 

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  • Sexually dimorphic gastrin-releasing peptide system in the lumbar spinal cord controls masculine reproductive functions in rats (性的二型を示す腰髄ガストリン放出ペプチド系は雄性性機能を制御する)

    第32回日本神経科学大会 (Neuroscience 2009)  2009年 

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  • ラット視床下部における膜結合型エストロゲン受容体(GPR30)の発現と細胞内局在

    日本動物学会中国四国支部大会  2009年 

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  • Distribution of G coupled receptor 30 and nuclear estrogen receptor alpha in the rat dorsal root ganglion

    13th Annual Meeting of the Society for Behavioral Neuroendocrinology (SBN)  2009年 

     詳細を見る

  • ラット脊髄後根神経節における膜結合型エストロゲン受容体GPR30の発現

    第114回日本解剖学会総会・全国学術集会  2009年 

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  • 性機能と gastrin-releasing peptide (GRP) ニューロンシステム

    第62回日本自律神経学会総会  2009年 

     詳細を見る

  • ラット腰髄におけるガストリン放出ペプチド系は性的二型であり、雄性性機能を制御する

    第35回日本神経内分泌学会  2008年 

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  • 雄性性機能を制御するラット腰髄ガストリン放出ペプチド系のストレス応答:心因性勃起障害治療への新たな展望

    第33回日本比較内分泌学会大会  2008年 

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  • Gastrin-releasing peptide system in the spinal cord controls the male sexual behavior

    US/JAPAN Neurosteroid Symposium 2008  2008年 

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  • ラット腰髄におけるガストリン放出ペプチドの局在は性的二型であり、その発現はアンドロゲン依存的に制御される (Sexually dimorphic gastrin releasing peptide expression is regulated by androgen in the lumbar spinal cord of male rats)

    第113回日本解剖学会総会・全国学術集会  2008年 

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  • The expression of the arginine vasopressin-enhanced green fluorescent protein fusion gene in the transgenic rat brain

    第7回国際下垂体後葉ホルモン会議  2007年 

     詳細を見る

  • Translocation of gold nanoparticles at the olfactory nerves around glomerulus layer of the ipsilateral olfactory bulb imaged by scaning TEM

    第37回北米神経科学大会  2007年 

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  • 扁桃体内神経回路のストレス応対に対する分子・形態変化

    第112回日本解剖学会総会・全国学術集会  2007年 

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  • PRP (platelet-rich plasma) enhances the initial tendon healing of circulation-derived mesenchymal cells; experimental study using bone marrow chimeric rat model

    第53回北米整形外科学会・学術集会  2007年 

     詳細を見る

  • バゾプレッシン-eGFPトランスジェニックラットにおけるGFP発現細胞の脳内分布についての検討

    第34回日本神経内分泌学会・学術集会  2007年 

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  • The vasopressin dynamism is altered by PTSD model stress

    第6回国際神経内分泌学会・学術集会  2006年 

     詳細を見る

  • 勃起を制御する局所神経回路とそのアンドロゲン応答

    特定領域「性分化機構の解明」第3回領域班会議  2006年 

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  • 勃起を制御する脊髄内局所神経回路

    特定領域「性分化機構の解明」第1回冬のワークショップ  2006年 

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  • Effects of single-prolonged stress on structural plasticity of neurons in the central and basolateral amygdala

    国際精神神経内分泌学シンポジウム  2006年 

     詳細を見る

  • Vasopressin dynamism in the supraoptic nucleus of PTSD model rat

    国際精神神経内分泌学シンポジウム  2006年 

     詳細を見る

  • GFP骨髄・腱キメラを用いた腱修復における未分化間葉細胞系細胞の起源の解析

    第111回日本解剖学会総会・全国学術集会  2006年 

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  • 多血小板血漿含浸ゼラチンハイドロゲル粒子の椎間板内投与による椎間板再生効果の組織学的検討

    第111回日本解剖学会総会・全国学術集会  2006年 

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  • PTSDストレスモデルによるバゾプレッシン系への影響

    第111回日本解剖学会総会・全国学術集会  2006年 

     詳細を見る

  • PTSDモデルラットを用いた扁桃体におけるニューロペプチドYの発現変化

    第111回日本解剖学会総会・全国学術集会  2006年 

     詳細を見る

  • PTSDモデルラットを用いた扁桃体ニューロンの形態変化に関する研究

    第111回日本解剖学会総会・全国学術集会  2006年 

     詳細を見る

  • 内分泌学的PTSDストレスモデルはバゾプレッシン系にも影響する

    第33回日本神経内分泌学会・学術集会  2006年 

     詳細を見る

  • ラット海馬における膜結合型エストロゲン受容体GPR30の発現と細胞内局在について

    第33回日本神経内分泌学会・学術集会  2006年 

     詳細を見る

  • PTSDモデルラットを用いた扁桃体ニューロンの形態変化に関する研究

    第29回日本神経科学大会  2006年 

     詳細を見る

  • オキシトシンニューロンにおける膜結合型エストロゲン受容体GPR30の発現と細胞内局在

    第33回日本神経内分泌学会・学術集会  2006年 

     詳細を見る

  • Distribution of gastrin releasing peptide in the rat lumbar spinal cord is sexually dimorphic and regulated by androgen

    第6回国際神経内分泌学会・学術集会  2006年 

     詳細を見る

▼全件表示

受賞

  • 日本神経内分泌学会 川上正澄賞

    2016年  

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    受賞国:日本国

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  • 岡山大学若手トップリサーチャー研究奨励賞

    2013年  

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    受賞国:日本国

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  • 日本動物学会奨励賞

    2012年  

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    受賞国:日本国

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  • The Japan Neuroscience Society Young Investigator Award 2010

    2010年  

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  • 日本神経科学学会奨励賞

    2010年  

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    受賞国:日本国

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  • 日本解剖学会奨励賞

    2010年  

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    受賞国:日本国

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  • 文部科学大臣表彰若手科学者賞

    2010年  

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    受賞国:日本国

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  • The Incitement Award of the Japanese Association of Anatomists in the fiscal year 2009

    2010年  

     詳細を見る

  • 第19回京都府立医科大学 学友会青蓮賞

    2009年  

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    受賞国:日本国

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  • 第8回日本神経内分泌学会若手研究奨励賞

    2008年  

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    受賞国:日本国

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▼全件表示

 

担当授業科目

  • 神経制御学演習 (2021年度) 通年  - その他

  • 神経生物学I (2021年度) 3・4学期  - [第3学期]水3,水4, [第4学期]水1,水2

  • 神経生物学IA (2021年度) 第3学期  - 水3,水4

  • 神経生物学II (2021年度) 1・2学期  - 月3,月4

  • 神経生物学IIA (2021年度) 第1学期  - 月3,月4

  • 神経生物学IIB (2021年度) 第2学期  - 月3,月4

  • 神経行動学 (2021年度) 後期  - 月1,月2

  • 神経行動学特論 (2021年度) 前期  - その他

  • 臨海先端実習 (2021年度) 集中  - その他

  • 臨海実習II (2021年度) 夏季集中  - その他

  • 臨海実習IV (2021年度) 夏季集中  - その他

  • 臨海実習V (2021年度) 夏季集中  - その他

  • 神経制御学演習 (2020年度) 通年  - その他

  • 神経生物学I (2020年度) 3・4学期  - [第3学期]水3,水4, [第4学期]水1,水2

  • 神経生物学IA (2020年度) 第3学期  - 水3,水4

  • 神経生物学II (2020年度) 1・2学期  - 月3,月4

  • 神経生物学IIA (2020年度) 第1学期  - 月3,月4

  • 神経生物学IIB (2020年度) 第2学期  - 月3,月4

  • 神経行動学 (2020年度) 後期  - 月1,月2

  • 神経行動学特論 (2020年度) 前期  - その他

  • 臨海先端実習 (2020年度) 集中  - その他

  • 臨海実習II (2020年度) 夏季集中  - その他

  • 臨海実習IV (2020年度) 夏季集中  - その他

  • 臨海実習V (2020年度) 夏季集中  - その他

▼全件表示