Faculty Profiles - SAKAMOTO Hirotaka

MISC - SAKAMOTO Hirotaka

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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

Estrogen regulate itch sensation

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

NEUROSCIENCE RESEARCH 68 E162 - E162 2010

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 ( 137 ) 146 - 148 2010

The neurobiology of psychogenic erectile dysfunction in the spinal cord

H. Sakamoto

Journal of Andrology 21 ( 4 ) 432 - 435 2010

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 2009.12

Language：English Publisher：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 2009.9

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

H. Sakamoto, M. Kawata

JOURNAL OF NEUROENDOCRINOLOGY 21 ( 4 ) 432 - 435 2009.4

Language：English Publishing type：Book review, literature introduction, etc. Publisher：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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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

Language：English Publisher：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

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 ( 135 ) 274 - 279 2009

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

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

バゾプレッシン(AVP)-eGFPトランスジェニックラットにおける青斑核での特異的なAVP-eGFPの合成

轟美和子, 上田陽一, 藤原広明, 大坪弘樹, 柴田美雅, 橋本弘史, 小林瑞, 坂本浩隆, 河田光博

日本病態生理学会雑誌 18 ( 2 ) 2009

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 2008.12

Language：English Publisher：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 2008.12

Language：English Publishing type：Book review, literature introduction, etc. Publisher：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 2008.10

Language：English Publisher：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 2008.8

Language：English Publisher：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 2008.6

Language：English Publishing type：Book review, literature introduction, etc. Publisher：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 2008.6

Language：English Publisher：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 2008.3

Language：English Publisher：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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