Updated on 2024/03/08

写真a

 
AIZAWA Sayaka
 
Organization
Faculty of Environmental, Life, Natural Science and Technology Associate Professor
Position
Associate Professor
Contact information
メールアドレス
External link

Degree

  • 博士(理学) ( 2012.3   埼玉大学 )

Research Interests

  • Circadian rhythm

  • Pituitary

  • Endocrinology

Research Areas

  • Life Science / Morphology and anatomical structure

  • Life Science / Molecular biology

  • Life Science / Metabolism and endocrinology

  • Life Science / Neurology

  • Life Science / Animal physiological chemistry, physiology and behavioral biology

Education

  • Saitama University   大学院理工学研究科  

    2009.4 - 2012.3

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    Country: Japan

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Research History

  • Okayama University   The Graduate School of Natural Science and Technology   Associate Professor

    2022.4

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    Country:Japan

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  • Okayama University   The Graduate School of Natural Science and Technology   Associate Professor

    2020.4 - 2022.3

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    Country:Japan

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  • Okayama University   The Graduate School of Natural Science and Technology   Assistant Professor

    2020.3

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    Country:Japan

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  • Okayama University   The Graduate School of Natural Science and Technology   Associate professor (tenure-track)

    2015.3 - 2020.2

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    Country:Japan

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  • Osaka University   Research Institute for Microbial Diseases   Post-doctoral researcher

    2013.3 - 2015.2

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    Country:Japan

    Notes:分子ウイルス研究室

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  • Saitama University   Graduate School of Science and Engineering   Post-doctoral researcher

    2012.4 - 2013.2

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    Country:Japan

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Professional Memberships

  • Japan Neuroendocrine Society

    2023

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  • Japanese Society for Chronobiology

    2018

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  • Endocrine Society

    2015

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  • The Society for Okayama Laboratory Animal Research

    2015

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  • The Zoological Society of Japan

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  • The Japan Society for Comparative Endocrinology

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  • The Japan Society for Pituitary Research

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Committee Memberships

  • The Japan Society for Comparative Endocrinology   Academic journal editorial board member  

    2021.1   

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  • The Japan Society for Comparative Endocrinology   Young Exchange Planning Committee  

    2019.1 - 2022.12   

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  • The Japan Society for Comparative Endocrinology   Coordinator  

    2019.1 - 2020.12   

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  • The Japan Society for Pituitary Research   Councilor  

    2016   

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    Committee type:Academic society

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Papers

  • Neuromedin U-deficient rats do not lose body weight or food intake. Reviewed International journal

    Kyoka Yokogi, Yuki Goto, Mai Otsuka, Fumiya Ojima, Tomoe Kobayashi, Yukina Tsuchiba, Yu Takeuchi, Masumi Namba, Mayumi Kohno, Minami Tetsuka, Sakae Takeuchi, Makoto Matsuyama, Sayaka Aizawa

    Scientific reports   12 ( 1 )   17472 - 17472   2022.10

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    Authorship:Last author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    Studies in genetically modified mice establish that essential roles of endogenous neuromedin U (NMU) are anorexigenic function and metabolic regulation, indicating that NMU is expected to be a potential target for anti-obesity agents. However, in central administration experiments in rats, inconsistent results have been obtained, and the essential role of NMU energy metabolism in rats remain unclear. This study aims to elucidate the role of endogenous NMU in rats. We generated NMU knockout (KO) rats that unexpectedly showed no difference in body weight, adiposity, circulating metabolic markers, body temperature, locomotor activity, and food consumption in both normal and high fat chow feeding. Furthermore, unlike reported in mice, expressions of Nmu and NMU receptor type 2 (Nmur2) mRNA were hardly detectable in the rat hypothalamic nuclei regulating feeding and energy metabolism, including the arcuate nucleus and paraventricular nucleus, while Nmu was expressed in pars tuberalis and Nmur2 was expressed in the ependymal cell layer of the third ventricle. These results indicate that the species-specific expression pattern of Nmu and Nmur2 may allow NMU to have distinct functions across species, and that endogenous NMU does not function as an anorexigenic hormone in rats.

    DOI: 10.1038/s41598-022-21764-6

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  • A regulatory mechanism of mouse kallikrein 1 gene expression by estrogen

    Takumi Iwasaki, Megumi Tokumori, Misaki Matsubara, Fumiya Ojima, Kana Kamigochi, Sayaka Aizawa, Maho Ogoshi, Atsushi P. Kimura, Sakae Takeuchi, Sumio Takahashi

    Molecular and Cellular Endocrinology   577   112044 - 112044   2023.11

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    Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.mce.2023.112044

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  • The suppressive effect of REVERBs on ghrelin and GOAT transcription in gastric ghrelin-producing cells Reviewed International journal

    Mio Iijima, Shota Takemi, Sayaka Aizawa, Takafumi Sakai, Ichiro Sakata

    Neuropeptides   90   102187 - 102187   2021.12

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    Ghrelin is a multifunctional gut peptide with a unique structure, which is modified by a medium chain fatty acid at the third serine by ghrelin O-acyl transferase (GOAT). It is well known that the major source of plasma ghrelin is the stomach, but the transcriptional regulation of gastric ghrelin and GOAT is incompletely understood. Here, we studied the involvement of the nuclear receptors REV-ERBα and REV-ERBβ on ghrelin and GOAT gene expression in vivo and in vitro. Reverse-transcriptase polymerase chain reaction analysis showed that REV-ERBα and REV-ERBβ mRNAs were expressed in the stomach and a stomach-derived ghrelin cell line (SG-1 cells). In vivo experiments with mice revealed the circadian rhythm of ghrelin, GOAT, and REV-ERBs. The peak expression of ghrelin and GOAT mRNAs occurred at Zeitgeber time (ZT) 4, whereas that of REV-ERBα and REV-ERBβ was observed at ZT8 and ZT12, respectively. Treatment of SG-1 cells with SR9009, a REV-ERB agonist, led to a significant reduction in ghrelin and GOAT mRNA levels. Overexpression of REV-ERBα and REV-ERBβ decreased ghrelin and GOAT mRNA levels in SG-1 cells. In contrast, small-interfering RNA (siRNA)-mediated double-knockdown of REV-ERBα and REV-ERBβ in SG-1 cells led to the upregulation in the expression of ghrelin and GOAT mRNAs. These results suggest that REV-ERBs suppress ghrelin and GOAT mRNA expression.

    DOI: 10.1016/j.npep.2021.102187

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  • Adrenomedullin 2 and 5 activate the calcitonin receptor-like receptor (clr) - Receptor activity-modifying protein 3 (ramp3) receptor complex in Xenopus tropicalis. Reviewed International journal

    Maho Ogoshi, Mikoto Takahashi, Kota Aoyagi, Kazuyoshi Ukena, Sayaka Aizawa, Hideaki Takeuchi, Sumio Takahashi, Sakae Takeuchi

    General and comparative endocrinology   306   113752 - 113752   2021.5

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    The adrenomedullin (AM) family is involved in diverse biological functions, including cardiovascular regulation and body fluid homeostasis, in multiple vertebrate lineages. The AM family consists of AM1, AM2, and AM5 in tetrapods, and the receptor for mammalian AMs has been identified as the complex of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 2 (RAMP2) or RAMP3. However, the receptors for AM in amphibians have not been identified. In this study, we identified the cDNAs encoding calcrl (clr), ramp2, and ramp3 receptor components from the western clawed frog (Xenopus tropicalis). Messenger RNAs of amphibian clr and ramp2 were highly expressed in the heart, whereas that of ramp3 was highly expressed in the whole blood. In HEK293T cells expressing clr-ramp2, cAMP response element luciferase (CRE-Luc) reporter activity was activated by am1. In HEK293T cells expressing clr-ramp3, CRE-Luc reporter activity was increased by the treatment with am2 at the lowest dose, but with am5 and am1 at higher dose. Our results provided new insights into the roles of AM family peptides through CLR-RAMP receptor complexes in the tetrapods.

    DOI: 10.1016/j.ygcen.2021.113752

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  • Adenosine stimulates neuromedin U mRNA expression in the rat pars tuberalis. Reviewed International journal

    Sayaka Aizawa, Tingting Gu, Arisa Kaminoda, Ryuya Fujioka, Fumiya Ojima, Ichiro Sakata, Takafumi Sakai, Maho Ogoshi, Sumio Takahashi, Sakae Takeuchi

    Molecular and cellular endocrinology   496   110518 - 110518   2019.10

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    Neuromedin U (NMU) shows circadian expression in the rat pars tuberalis (PT), and is known to be suppressed by melatonin. Here we examined the involvement of adenosine in the regulation of Nmu expression. We found that the rat PT expressed adenosine receptor A2b and that an adenosine receptor agonist, NECA, stimulated Nmu expression in brain slice cultures. In vitro promoter assays revealed that NECA stimulated Nmu promoter activity via a cAMP response element (CRE) in the presence of adenosine receptor A2b. NECA also increased the levels of phosphorylated CRE-binding protein. These findings suggest that adenosine stimulates Nmu expression by activating the cAMP signaling pathway through adenosine receptor A2b in the rat PT. This is the first report to demonstrate that Nmu expression in the PT is regulated by adenosine, which acts as an intravital central metabolic signal, in addition to melatonin, which acts as an external photoperiodic environmental signal.

    DOI: 10.1016/j.mce.2019.110518

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  • Changes in prolactin receptor homodimer availability may cause late feathering in chickens. Reviewed International journal

    Ayako Okamura, Ayane Masumoto, Atsushi Takenouchi, Toshiyuki Kudo, Sayaka Aizawa, Maho Ogoshi, Sumio Takahashi, Masaoki Tsudzuki, Sakae Takeuchi

    General and comparative endocrinology   272   109 - 116   2019.2

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    Chicken early (EF) and late feathering (LF) are sex-linked phenotypes conferred by wild-type k+ and dominant K alleles on chromosome Z, respectively. Besides prolactin (PRL) receptor (PRLR) and sperm flagellar 2 (SPEF2) genes, the K allele contains a fusion gene in which partially duplicated PRLR (dPRLR) and SPEF2 (dSPEF2) genes are linked in a tail-to-tail manner. The causative dPRLR gene encodes a C-terminal truncated receptor. LF chickens have short or no primaries at hatching; however, their feather growth rate is higher than that of EF chickens. This study aimed to elucidate the molecular basis of the K allele's biphasic effect on feather development. By 3'RACE and RT-PCR analyses, we demonstrated that dSPEF2 gene transcription occurred beyond all coding exons of the dPRLR gene on the opposite strand and that dPRLR mRNA was less abundant than PRLR mRNA. In addition, a 5'UTR splice variant (SPV) of PRL receptor mRNAs was increased in LF chickens. In vitro expression analysis of 5'UTR linked to the luciferase reporter gene revealed higher translation efficiency of SPV. RT-qPCR showed that the dPRLR mRNA level was higher in embryos; conversely, SPV was higher in hatched chickens, as was dSPEF2 mRNA. These findings suggest that the K allele inhibits feather development at the fetal stage by expressing dPRLR to attenuate PRLR function and promotes feather growth after hatching by increasing PRLR through dSPEF2 mRNA expression. Increased SPV may cause greater feather growth than that in EF chickens by increasing the availability of PRLR homodimers and enhancing PRL signaling.

    DOI: 10.1016/j.ygcen.2018.12.011

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  • β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification. Reviewed International journal

    Chika Ikenoya, Shota Takemi, Arisa Kaminoda, Sayaka Aizawa, Shiomi Ojima, Zhi Gong, Rakhi Chacrabati, Daisuke Kondo, Reiko Wada, Toru Tanaka, Sachiko Tsuda, Takafumi Sakai, Ichiro Sakata

    Scientific reports   8 ( 1 )   9176 - 9176   2018.6

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    Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.

    DOI: 10.1038/s41598-018-27458-2

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  • Milk basic protein increases ghrelin secretion and bone mineral density in rodents Reviewed

    Yuko Ishida, Rakhi Chacrabati, Aiko Ono-Ohmachi, Zhi Gong, Chika Ikenoya, Sayaka Aizawa, Takayuki Y. Nara, Yoshikazu Morita, Ken Kato, Takafumi Sakai, Ichiro Sakata

    Nutrition   39-40   15 - 19   2017.7

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    DOI: 10.1016/j.nut.2017.02.003

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  • Identification of marker genes for pars tuberalis morphogenesis in chick embryo: expression of Cytokine-like 1 and Gap junction protein alpha 5 in pars tuberalis. Reviewed International journal

    Sayaka Aizawa, Yuriko Higaki, Amrita Dudaui, Mai Nagasaka, Sumio Takahashi, Ichiro Sakata, Takafumi Sakai

    Cell and tissue research   366 ( 3 )   721 - 731   2016.12

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    The adenohypophysis is formed from the oral ectoderm and consists of the pars distalis (PD), pars intermedia, and pars tuberalis (PT). The mechanisms of PD development have been extensively studied, and the cellular differentiation of the PD is well understood. However, the morphogenesis and differentiation of the PT are still unclear, and the genes expressed during PT development remain largely unknown. We have explored genes specifically expressed in the PT during embryonic development and analyzed their spatiotemporal expression patterns. Microarray analysis of laser-captured PT and PD tissues obtained from chick embryos on embryonic day 10 (E10.0) has shown high expression of Cytokine-like 1 (CYTL1) and Gap junction protein alpha 5 (GJA5) genes in the PT. Detailed analysis of these spatiotemporal expression patterns during chick embryo development by in situ hybridization has revealed that CYTL1 mRNA first appears in the lateral head ectoderm and ventral head ectoderm at E1.5. The expression of CYTL1 moves into Rathke's pouch at E2.5 and is then localized in the PT primordium where it is continuously expressed until E12.0. GJA5 mRNA is transiently detected in the PT primordium from E6.0 to E12.0, whereas its expression is not detected in the PD during development. Thus, these genes might be involved in the regulation mechanisms of PT development and could be useful markers for PT development.

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  • The proximal gastric corpus is the most responsive site of motilin-induced contractions in the stomach of the Asian house shrew. Reviewed International journal

    Amrita Dudani, Sayaka Aizawa, Gong Zhi, Toru Tanaka, Takamichi Jogahara, Ichiro Sakata, Takafumi Sakai

    Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology   186 ( 5 )   665 - 75   2016.7

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    The migrating motor complex (MMC) is responsible for emptying the stomach during the interdigestive period, in preparation for the next meal. It is known that gastric phase III of MMC starts from the proximal stomach and propagates the contraction downwards. We hypothesized that a certain region of the stomach must be more responsive to motilin than others, and that motilin-induced strong gastric contractions propagate from that site. Stomachs of the Suncus or Asian house shrew, a small insectivorous mammal, were dissected and the fundus, proximal corpus, distal corpus, and antrum were examined to study the effect of motilin using an organ bath experiment. Motilin-induced contractions differed in different parts of the stomach. Only the proximal corpus induced gastric contraction even at motilin 10(-10) M, and strong contraction was induced by motilin 10(-9) M in all parts of the stomach. The GPR38 mRNA expression was also higher in the proximal corpus than in the other sections, and the lowest expression was observed in the antrum. GPR38 mRNA expression varied with low expression in the mucosal layer and high expression in the muscle layer. Additionally, motilin-induced contractions in each dissected part of the stomach were inhibited by tetrodotoxin and atropine pretreatment. These results suggest that motilin reactivity is not consistent throughout the stomach, and an area of the proximal corpus including the cardia is the most sensitive to motilin.

    DOI: 10.1007/s00360-016-0985-1

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  • TRC8-dependent degradation of hepatitis C virus immature core protein regulates viral propagation and pathogenesis. Reviewed International journal

    Sayaka Aizawa, Toru Okamoto, Yukari Sugiyama, Takahisa Kouwaki, Ayano Ito, Tatsuya Suzuki, Chikako Ono, Takasuke Fukuhara, Masahiro Yamamoto, Masayasu Okochi, Nobuhiko Hiraga, Michio Imamura, Kazuaki Chayama, Ryosuke Suzuki, Ikuo Shoji, Kohji Moriishi, Kyoji Moriya, Kazuhiko Koike, Yoshiharu Matsuura

    Nature communications   7   11379 - 11379   2016.5

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    Signal-peptide peptidase (SPP) is an intramembrane protease that participates in the production of the mature core protein of hepatitis C virus (HCV). Here we show that SPP inhibition reduces the production of infectious HCV particles and pathogenesis. The immature core protein produced in SPP-knockout cells or by treatment with an SPP inhibitor is quickly degraded by the ubiquitin-proteasome pathway. Oral administration of the SPP inhibitor to transgenic mice expressing HCV core protein (CoreTg) reduces the expression of core protein and ameliorates insulin resistance and liver steatosis. Moreover, the haploinsufficiency of SPP in CoreTg has similar effects. TRC8, an E3 ubiquitin ligase, is required for the degradation of the immature core protein. The expression of the HCV core protein alters endoplasmic reticulum (ER) distribution and induces ER stress in SPP/TRC8 double-knockout cells. These data suggest that HCV utilizes SPP cleavage to circumvent the induction of ER stress in host cells.

    DOI: 10.1038/ncomms11379

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  • Rikkunshitoinduces gastric relaxationviatheβ-adrenergic pathway inSuncus murinus Reviewed

    A. Mondal, A. Takehara, S. Aizawa, T. Tanaka, N. Fujitsuka, T. Hattori, T. Sakai, I. Sakata

    Neurogastroenterology & Motility   27 ( 6 )   875 - 884   2015.6

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    Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/nmo.12564

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  • G protein-coupled receptor 120 signaling regulates ghrelin secretion in vivo and in vitro. Reviewed International journal

    Zhi Gong, Makoto Yoshimura, Sayaka Aizawa, Reiko Kurotani, Jeffrey M Zigman, Takafumi Sakai, Ichiro Sakata

    American journal of physiology. Endocrinology and metabolism   306 ( 1 )   E28-35   2014.1

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    Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is produced predominantly in the stomach. It has been reported that endogenous ghrelin levels are increased by fasting and decreased immediately after feeding and that fasting-induced ghrelin release is controlled by the sympathetic nervous system. However, the mechanisms of plasma ghrelin decrement after feeding are poorly understood. Here, we studied the control of ghrelin secretion using ghrelin-producing cell lines and found that these cells express high levels of mRNA encoding G-protein coupled receptor 120 (GPR120). Addition of GW-9508 (a GPR120 chemical agonist) and α-linolenic acid (a natural ligand for GPR120) inhibited the secretion of ghrelin by ∼50 and 70%, respectively. However, the expression levels of preproghrelin and ghrelin O-acyltransferase (GOAT) mRNAs were not influenced by GW-9508. In contrast, the expression levels of prohormone convertase 1 were decreased significantly by GW-9508 incubation. Moreover, we observed that the inhibitory effect of GW-9508 on ghrelin secretion was blocked by a small interfering RNA (siRNA) targeting the sequence of GPR120. Furthermore, pretreatment with GW-9508 blocked the effect of the norepinephrine (NE)-induced ghrelin elevation in ghrelin cell lines. In addition, we showed that GW-9508 inhibited ghrelin secretion via extracellular signal-regulated kinase activity in ghrelin cell lines. Finally, we found that GW-9508 decreased plasma ghrelin levels in mice. These results suggest that the decrease of ghrelin secretion after feeding is induced partially by long-chain fatty acids that act directly on gastric GPR120-expressing ghrelin cells.

    DOI: 10.1152/ajpendo.00306.2013

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  • Detailed morphogenetic analysis of the embryonic chicken pars tuberalis as glycoprotein alpha subunit positive region. Reviewed International journal

    Makiko Inoue, Sayaka Aizawa, Yuriko Higaki, Akira Kawashima, Kanako Koike, Hiroyasu Takagi, Takafumi Sakai, Ichiro Sakata

    Journal of molecular histology   44 ( 4 )   401 - 9   2013.8

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    The pars tuberalis (PT) is a part of the anterior pituitary gland that is located as a thin cell layer surrounding the median eminence. The characteristics of PT, including cell shape and cell composition, differ from those of the pars distalis (PD), suggesting that PT has unique physiological functions and different morphogenesis compared to PD. In this study, we used chicken embryos and showed for the first time that most hormone-producing cells in PT at embryonic day (E) 20.0 were only glycoprotein α subunit (αGSU)-positive staining cells. Then, using serial frontal and sagittal sections, we examined the detailed distribution of the αGSU mRNA-expressing region, as a marker of PT in the chicken embryonic pituitary gland during the E3.0-20.0 period. This three-dimensional expression pattern analysis clarified that αGSU mRNA expression initially appeared only in the bilateral regions of the Rathke's recess (RR) at E3.5, and this region expanded and showed a ring-like structure on RR. Subsequently, this αGSU mRNA-expressing region gradually expanded upward and reached the diencephalon at E8.0. This region became thinner as it surrounded the base of the diencephalon from E12.0 to E20.0. In this study, we demonstrated the detailed morphological changes of the chicken PT primordium by detecting αGSU mRNA, and we also showed that PT is a unique region in the early developmental stage.

    DOI: 10.1007/s10735-012-9479-y

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  • The role of the vagus nerve in the migrating motor complex and ghrelin- and motilin-induced gastric contraction in suncus. Reviewed International journal

    Yuki Miyano, Ichiro Sakata, Kayuri Kuroda, Sayaka Aizawa, Toru Tanaka, Takamichi Jogahara, Reiko Kurotani, Takafumi Sakai

    PloS one   8 ( 5 )   e64777   2013

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    The upper gastrointestinal (GI) tract undergoes a temporally coordinated cyclic motor pattern known as the migrating motor complex (MMC) in both dogs and humans during the fasted state. Feeding results in replacement of the MMC by a pattern of noncyclic, intermittent contractile activity termed as postprandial contractions. Although the MMC is known to be stimulated by motilin, recent studies have shown that ghrelin, which is from the same peptide family as motilin, is also involved in the regulation of the MMC. In the present study, we investigated the role of the vagus nerve on gastric motility using conscious suncus-a motilin- and ghrelin-producing small animal. During the fasted state, cyclic MMC comprising phases I, II, and III was observed in both sham-operated and vagotomized suncus; however, the duration and motility index (MI) of phase II was significantly decreased in vagotomized animals. Motilin infusion (50 ng·kg(-1)·min(-1) for 10 min) during phase I had induced phase III-like contractions in both sham-operated and vagotomized animals. Ghrelin infusion (0.1, 0.3, 1, 3, or 10 µg·kg(-1)·min(-1) for 10 min) enhanced the amplitude of phase II MMC in sham-operated animals, but not in vagotomized animals. After feeding, phase I was replaced by postprandial contractions, and motilin infusion (50 ng·kg(-1)·min(-1) for 10 min) did not induce phase III-like contractions in sham-operated suncus. However, in vagotomized suncus, feeding did not evoke postprandial contractions, but exogenous motilin injection strongly induced phase III-like contractions, as noted during the phase I period. Thus, the results indicate that ghrelin stimulates phase II of the MMC via the vagus nerve in suncus. Furthermore, the vagus nerve is essential for initiating postprandial contractions, and inhibition of the phase III-like contractions induced by motilin is highly dependent on the vagus nerve.

    DOI: 10.1371/journal.pone.0064777

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  • Mechanism of ghrelin-induced gastric contractions in Suncus murinus (house musk shrew): involvement of intrinsic primary afferent neurons. Reviewed International journal

    Anupom Mondal, Sayaka Aizawa, Ichiro Sakata, Chayon Goswami, Sen-ichi Oda, Takafumi Sakai

    PloS one   8 ( 4 )   e60365   2013

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    Here, we have reported that motilin can induce contractions in a dose-dependent manner in isolated Suncus murinus (house musk shrew) stomach. We have also shown that after pretreatment with a low dose of motilin (10(-10) M), ghrelin also induces gastric contractions at levels of 10(-10) M to 10(-7) M. However, the neural mechanism of ghrelin action in the stomach has not been fully revealed. In the present study, we studied the mechanism of ghrelin-induced contraction in vitro using a pharmacological method. The responses to ghrelin in the stomach were almost completely abolished by hexamethonium and were significantly suppressed by the administration of phentolamine, prazosin, ondansetron, and naloxone. Additionally, N-nitro-l-arginine methylester significantly potentiated the contractions. Importantly, the mucosa is essential for ghrelin-induced, but not motilin-induced, gastric contractions. To evaluate the involvement of intrinsic primary afferent neurons (IPANs), which are multiaxonal neurons that pass signals from the mucosa to the myenteric plexus, we examined the effect of the IPAN-related pathway on ghrelin-induced contractions and found that pretreatment with adenosine and tachykinergic receptor 3 antagonists (SR142801) significantly eliminated the contractions and GR113808 (5-hydroxytryptamine receptor 4 antagonist) almost completely eliminated it. The results indicate that ghrelin stimulates and modulates suncus gastric contractions through cholinergic, adrenergic, serotonergic, opioidergic neurons and nitric oxide synthases in the myenteric plexus. The mucosa is also important for ghrelin-induced gastric contractions, and IPANs may be the important interneurons that pass the signal from the mucosa to the myenteric plexus.

    DOI: 10.1371/journal.pone.0060365

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  • Negative regulation of neuromedin U mRNA expression in the rat pars tuberalis by melatonin. Reviewed International journal

    Sayaka Aizawa, Ichiro Sakata, Mai Nagasaka, Yuriko Higaki, Takafumi Sakai

    PloS one   8 ( 7 )   e67118   2013

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    The pars tuberalis (PT) is part of the anterior pituitary gland surrounding the median eminence as a thin cell layer. The characteristics of PT differ from those of the pars distalis (PD), such as cell composition and gene expression, suggesting that the PT has a unique physiological function compared to the PD. Because the PT highly expresses melatonin receptor type 1, it is considered a mediator of seasonal and/or circadian signals of melatonin. Expression of neuromedin U (NMU) that is known to regulate energy balance has been previously reported in the rat PT; however, the regulatory mechanism of NMU mRNA expression and secretion in the PT are still obscure. In this study, we examined both the diurnal change of NMU mRNA expression in the rat PT and the effects of melatonin on NMU in vivo. In situ hybridization and quantitative PCR analysis of laser microdissected PT samples revealed that NMU mRNA expression in the PT has diurnal variation that is high during the light phase and low during the dark phase. Furthermore, melatonin administration significantly suppressed NMU mRNA expression in the PT in vivo. On the other hand, 48 h fasting did not have an effect on PT-NMU mRNA expression, and the diurnal change of NMU mRNA expression was maintained. We also found the highest expression of neuromedin U receptor type 2 (NMUR2) mRNA in the third ventricle ependymal cell layer, followed by the arcuate nucleus and the spinal cord. These results suggest that NMU mRNA expression in the PT is downregulated by melatonin during the dark phase and shows diurnal change. Considering that NMU mRNA in the PT showed the highest expression level in the brain, PT-NMU may act on NMUR2 in the brain, especially in the third ventricle ependymal cell layer, with a circadian rhythm.

    DOI: 10.1371/journal.pone.0067118

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  • Ghrelin increases intracellular Ca²⁺ concentration in the various hormone-producing cell types of the rat pituitary gland. Reviewed International journal

    Mami Yamazaki, Sayaka Aizawa, Toru Tanaka, Takafumi Sakai, Ichiro Sakata

    Neuroscience letters   526 ( 1 )   29 - 32   2012.9

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    Ghrelin, isolated from the stomach as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), has potent growth hormone release ability in vivo and in vitro. Although GHS-R is abundantly expressed in the pituitary gland, there is no direct evidence of a relationship between hormone-producing cells and functional GHS-R in the pituitary gland. The aim of this study was to determine which anterior pituitary cells respond to ghrelin stimulation in male rats. We performed Fura-2 Ca(2+) imaging analysis using isolated pituitary cells, and performed immunocytochemistry to identify the type of pituitary hormone-producing cells. In Fura-2 Ca(2+) imaging analysis, ghrelin administration increased the intracellular Ca(2+) concentration in approximately 50% of total isolated anterior pituitary cells, and 20% of these cells strongly responded to ghrelin. Immunocytochemical analysis revealed that 82.9 ± 1.3% of cells that responded to ghrelin stimulation were GH-immunopositive. On the other hand, PRL-, LH-, and ACTH-immunopositive cells constituted 2.0 ± 0.3%, 12.6 ± 0.3%, and 2.5 ± 0.8% of ghrelin-responding pituitary cells, respectively. TSH-immunopositive cells did not respond to ghrelin treatment. These results suggest that ghrelin directly acts not only on somatotrophs, but also on mammotrophs, gonadotrophs, and corticotrophs in the rat pituitary gland.

    DOI: 10.1016/j.neulet.2012.07.063

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  • Molecular identification of GHS-R and GPR38 in Suncus murinus. Reviewed International journal

    Airi Suzuki, Yuko Ishida, Sayaka Aizawa, Ichiro Sakata, Chihiro Tsutsui, Anupom Mondal, Koike Kanako, Takafumi Sakai

    Peptides   36 ( 1 )   29 - 38   2012.7

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    We previously identified ghrelin and motilin genes in Suncus murinus (suncus), and also revealed that motilin induces phase III-like strong contractions in the suncus stomach in vivo, as observed in humans and dogs. Moreover, repeated migrating motor complexes were found in the gastrointestinal tract of suncus at regular 120-min intervals. We therefore proposed suncus as a small laboratory animal model for the study of gastrointestinal motility. In the present study, we identified growth hormone secretagogue receptor (GHS-R) and motilin receptor (GPR38) genes in the suncus. We also examined their tissue distribution throughout the body. The amino acids of suncus GHS-R and GPR38 showed high homology with those of other mammals and shared 42% amino acid identity. RT-PCR showed that both the receptors were expressed in the hypothalamus, medulla oblongata, pituitary gland and the nodose ganglion in the central nervous system. In addition, GHS-R mRNA expressions were detected throughout the stomach and intestine, whereas GPR38 was expressed in the gastric muscle layer, lower intestine, lungs, heart, and pituitary gland. These results suggest that ghrelin and motilin affect gut motility and energy metabolism via specific receptors expressed in the gastrointestinal tract and/or in the central nervous system of suncus.

    DOI: 10.1016/j.peptides.2012.04.019

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  • Detailed analysis of the δ-crystallin mRNA-expressing region in early development of the chick pituitary gland. Reviewed International journal

    Makiko Inoue, Tomoya Shiina, Sayaka Aizawa, Ichiro Sakata, Hiroyasu Takagi, Takafumi Sakai

    Journal of molecular histology   43 ( 3 )   273 - 80   2012.6

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    Although δ-crystallin (δ-crys), also known as lens protein, is transiently expressed in Rathke's pouch (RP) of the chick embryo, detailed temporal and spatial expression patterns have been obscure. In this study, to understand the relationship between the δ-crys mRNA-expressing region and RP formation, we examined the embryonic expression pattern of δ-crys mRNA in the primordium of the adenohypophysis. δ-crys mRNA expression was initially found at stage 15 anterior to the foregut and posterior to the invaginated oral ectoderm. After RP formation, the δ-crys mRNA was expressed in the post-ventral region of RP and the anterior region of RP. δ-crys mRNA expression was then restricted to the cephalic lobe of the pituitary gland. From stage 20, the δ-crys and alpha-glycoprotein subunit (αGSU) mRNA-expressing regions were almost completely overlapping. The αGSU mRNA-expressing region is thought to be the primordium of the pars tuberalis, and these regions were overlapped with the Lhx3 mRNA-expressing region. The intensity of δ-crys mRNA expression gradually decreased with development and completely disappeared by stage 34. These results suggest that the embryonic chick pituitary gland consists of two different regions labeled with δ-crys and Lhx3.

    DOI: 10.1007/s10735-012-9407-1

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  • Coordination of motilin and ghrelin regulates the migrating motor complex of gastrointestinal motility in Suncus murinus. Reviewed International journal

    Anupom Mondal, Zuoyun Xie, Yuki Miyano, Chihiro Tsutsui, Ichiro Sakata, Yoichi Kawamoto, Sayaka Aizawa, Toru Tanaka, Sen-ichi Oda, Takafumi Sakai

    American journal of physiology. Gastrointestinal and liver physiology   302 ( 10 )   G1207-15   2012.5

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    Motilin and ghrelin are the gastrointestinal (GI) hormones released in a fasting state to stimulate the GI motility of the migrating motor complex (MMC). We focused on coordination of the ghrelin/motilin family in gastric contraction in vivo and in vitro using the house musk shrew (Suncus murinus), a ghrelin- and motilin-producing mammal. To measure the contractile activity of the stomach in vivo, we recorded GI contractions either in the free-moving conscious or anesthetized S. murinus and examined the effects of administration of motilin and/or ghrelin on spontaneous MMC in the fasting state. In the in vitro study, we also studied the coordinative effect of these hormones on the isolated stomach using an organ bath. In the fasting state, phase I, II, and III contractions were clearly recorded in the gastric body (as observed in humans and dogs). Intravenous infusion of ghrelin stimulated gastric contraction in the latter half of phase I and in the phase II in a dose-dependent manner. Continuous intravenous infusion of ghrelin antagonist (d-Lys3-GHRP6) significantly suppressed spontaneous phase II contractions and prolonged the time of occurrence of the peak of phase III contractions. However, intravenous infusion of motilin antagonist (MA-2029) did not inhibit phase II contractions but delayed the occurrence of phase III contractions of the MMC. In the in vitro study, even though a high dose of ghrelin did not stimulate contraction of stomach preparations, ghrelin administration (10(-10)-10(-7) M) with pretreatment of a low dose of motilin (10(-10) M) induced gastric contraction in a dose-dependent manner. Pretreatment with 10(-8) M ghrelin enhanced motilin-stimulated gastric contractions by 10 times. The interrelation of these peptides was also demonstrated in the anesthetized S. murinus. The results suggest that ghrelin is important for the phase II contraction and that coordination of motilin and ghrelin are necessary to initiate phase III contraction of the MMC.

    DOI: 10.1152/ajpgi.00379.2011

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  • Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis. Reviewed International journal

    Sayaka Aizawa, Takafumi Sakai, Ichiro Sakata

    The Journal of endocrinology   212 ( 3 )   383 - 94   2012.3

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    Thyroid-stimulating hormone (TSH)-producing cells of the pars tuberalis (PT) display distinct characteristics that differ from those of the pars distalis (PD). The mRNA expression of TSHβ and αGSU in PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism for TSHβ expression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on laser-captured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of the KA2, which is an ionotropic glutamic acid receptor (iGluR). In addition, the amino acid transporter A2 (ATA2), also known as the glutamine transporter, and glutaminase (GLS), as well as GLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid on TSHβ expression and αGSU expression in PT slice cultures. l-Glutamine and l-glutamic acid significantly stimulated TSHβ expression in PT slices after 2- and 4-h treatments, and the effect of l-glutamic acid was stronger than that of l-glutamine. In contrast, treatment with glutamine and glutamic acid did not affect αGSU expression in the PT or the expression of TSHβ or αGSU in the PD. These results strongly suggest that glutamine is taken up by PT cells through ATA2 and that glutamic acid locally converted from glutamine by Gls induces TSHβ expression via the KA2 in an autocrine and/or paracrine manner in the PT.

    DOI: 10.1530/JOE-11-0388

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  • Expression of a thyroglobulin (Tg) variant in mouse kidney glomerulus Reviewed

    Huhehasi Wu, Sayuri Suzuki, Donald F. Sellitti, Sonia Q. Doi, Kazunari Tanigawa, Sayaka Aizawa, Takeshi Akama, Akira Kawashima, Masayo Mishima, Norihisa Ishii, Akio Yoshida, Ichiro Hisatome, Nancy L. Koles, Ryohei Katoh, Koichi Suzuki

    Biochemical and Biophysical Research Communications   389 ( 2 )   269 - 273   2009.11

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    DOI: 10.1016/j.bbrc.2009.08.129

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  • マウス腎臓におけるサイログロブリン遺伝子断片の発現と意義

    Wu Huhehasi, 鈴木 さゆり, Sellitti Donald, Doi Sonia, 赤間 剛, 相沢 清香, 川島 晃, 谷川 和也, 吉田 明雄, 加藤 良平, 鈴木 幸一

    日本内分泌学会雑誌   85 ( 2 )   784 - 785   2009.9

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  • 腎メサンジウム細胞に発現するサイログロブリン遺伝子産物のクローニング 甲状腺自己免疫と糸球体腎炎とのリンク

    Wu Huhehasi, 赤間 剛, 相沢 清香, 川島 晃, 谷川 和也, 吉田 明雄, 鈴木 幸一

    日本内分泌学会雑誌   84 ( 1 )   210 - 210   2008.4

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  • Diurnal Change of Thyroid-Stimulating Hormone mRNA Expression in the Rat Pars Tuberalis Reviewed

    S. Aizawa, S. Hoshino, I. Sakata, A. Adachi, S. Yashima, A. Hattori, T. Sakai

    Journal of Neuroendocrinology   19 ( 11 )   839 - 846   2007.11

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    DOI: 10.1111/j.1365-2826.2007.01603.x

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Books

  • The latest technology in genome editing and its application in pharmaceuticals, gene therapy, agriculture, aquatic and livestock products, and the production of useful substances

    ( Role: Joint author)

    Technical information institute co., Ltd  2023.8  ( ISBN:9784861049781

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    CiNii Books

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  • Glutamine in Health and Disease

    ( Role: Contributor ,  The role of glutamine and glutamic acid in the pituitary gland: Involvement of TSH in pars tuberalis.)

    2015 

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  • Neuromedin U Invited Reviewed

    Bioscience & Industry   81 ( 3 )   224 - 225   2023.5

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  • ツメガエル属におけるAdrenomedullin 5の局在と免疫に関する機能

    御輿真穂, 御輿真穂, 山浦晋平, 青柳康太, 荒木文平, 相澤清香, 相澤清香, 竹内栄, 竹内栄, 高橋純夫, 高橋純夫

    岡山実験動物研究会報   ( 35 )   2019

  • ニワトリにおける遅羽性K遺伝子の作用メカニズムの解析

    岡村彩子, 増本絢音, 竹之内惇, 相澤清香, 御輿真穂, 御輿真穂, 高橋純夫, 高橋純夫, 都築政起, 竹内栄, 竹内栄

    岡山実験動物研究会報   ( 34 )   2018

  • ラット隆起部におけるニューロメジンUの発現とその制御メカニズム

    相澤清香, 顧ていてい, 神之田有紗, 藤岡竜矢, 御輿真穂, 竹内栄, 高橋純夫

    岡山実験動物研究会報   ( 34 )   2018

  • ラット脳下垂体隆起部の新規生理機能の探索

    相澤清香, 坂井田初季, 坂田一郎, 坂井貴文, 御輿真穂, 竹内栄, 高橋純夫

    岡山実験動物研究会報   ( 33 )   2017

  • マウス子宮内膜におけるTGF-β遺伝子の発現制御

    吉田すみれ, 相澤清香, 御輿真穂, 竹内栄, 高橋純夫

    岡山実験動物研究会報   ( 33 )   2017

  • Identification of Marker Gene of Pars Tuberalis Morphogenesis in Chicken Embryo. The expression of Cytokine-like 1 and Gap junction protein alpha 5 in the pars tuberalis

    相澤清香, 檜垣佑理子, 御輿真穂, 竹内栄, 高橋純夫

    岡山実験動物研究会報   ( 33 )   2017

  • ウズラPBCF遺伝子の構造と発現

    釘本綾子, 相澤清香, 御輿真穂, 高橋純夫, 竹内栄

    岡山実験動物研究会報   ( 32 )   2016

  • Mechanism of Rikkunshito-Induced Gastric Relaxation in Suncus Murinus Through the beta-Adrenergic Pathway

    Anupom Mondal, Amane Takehara, Sayaka Aizawa, Toru Tanaka, Naoki Fujitsuka, Tomohisa Hattori, Takafumi Sakai, Ichiro Sakata

    GASTROENTEROLOGY   148 ( 4 )   S893 - S893   2015.4

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  • Motilin and Ghrelin Additively Stimulate Gastric Acid Secretion in Suncus Murinus

    Ichiro Sakata, Yoshiaki Shimada, Toru Tanaka, Kanako Koike, Sayaka Aizawa, Takafumi Sakai

    GASTROENTEROLOGY   144 ( 5 )   S711 - S711   2013.5

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  • らい菌は宿主マクロファージのTLRシグナルを抑制し細胞内寄生環境を構築する

    谷川和也, 鈴木幸一, 川島晃, WU Huhehasi, 赤間剛, 林もゆる, 中村和昭, 相沢清香, BANG Pham Dang, 石藤雄子, 木村博昭, 生山祥一郎, 武下文彦, 石井則久

    Jpn J Lepr   78 ( 2 )   138 - 138   2009.4

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Presentations

  • Functional analysis of neuromedin U in the rat: stress response and anxiety behavior

    Sayaka Aizawa

    47th The Japan Society for Comparative Endocrinology  2023.11.18 

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    Event date: 2023.11.17 - 2023.11.19

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  • Effects of neuromedin U on testosterone circadian rhythm formation and wheel running activity

    Mai Ootsuka, Sakae Takeuchi, Makoto Matsuyama, Sayaka Aizawa

    47th The Japan Society for Comparative Endocrinology  2023.11.17 

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    Event date: 2023.11.17 - 2023.11.19

    Presentation type:Oral presentation (general)  

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  • Analysis of the circadian rhythm of neuromedin U expression in the rat pituitary pars tuberalis and its control mechanism by melatonin

    Sayaka Aizawa

    94th The Zoological Society of Japan  2023.9.7 

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    Event date: 2023.9.7 - 2023.9.10

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  • ラットのニューロメジンUはテストステロン産生の制御を介して自発活動に影響を及ぼす

    大塚 舞, 竹内 優羽, 手塚 都仁, 森山 真帆, 大野 百合香, 木下 あすか, 竹内 栄, 松山 誠, 相澤 清香

    日本動物学会 第94回山形大会  2023.9.7 

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    Event date: 2023.9.7 - 2023.9.9

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  • In silico and in vitro analysis of transcriptional regulation. Invited

    94th The Zoological Society of Japan  2023.9.7 

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    Event date: 2023.9.7 - 2023.9.9

    Presentation type:Symposium, workshop panel (public)  

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  • Novel functions of Neuromedin U in behavioral motivation.

    Sayaka Aizawa

    46th The Japan Society for Comparative Endocrinology 

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    Event date: 2022.10.28 - 2022.10.30

    Presentation type:Poster presentation  

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  • Effect of Neuromedin U deficiency on spontaneous activity

    93rd The Zoological Society of Japan  2022.9 

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    Event date: 2022.9.8 - 2022.9.10

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  • Characterization of the chicken ASIP gene products

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    Event date: 2022.9.8 - 2022.9.10

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  • Neuromedin U deficiency reduces running wheel activity in male rats

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    Event date: 2022.5.21 - 2022.5.22

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  • ラット下垂体隆起部におけるニューロメジンUの概日リズム発現の制御機構

    相澤清香, 顧婷婷, 神之田有紗, 原田有希菜, 高橋純夫, 竹内栄

    第26回学術大会日本時計生物学会(金沢市)  2019.10.12 

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    Event date: 2019.10.12 - 2019.10.13

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  • ラット下垂体隆起部におけるニューロメジンUの概日リズム発現の制御機構

    相澤清香, 神之田有紗, 原田有希菜, 高橋純夫, 竹内栄

    日本動物学会第89回大阪大会(大阪市) 

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    Event date: 2019.9.12 - 2019.9.14

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  • Analysis of new functions using Neuromedin U-deficient rats Invited

    Sayaka Aizawa

    The 17th Rat Resource and Research Meeting  2024.1.26 

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  • Role of neuromedin U on testosterone secretion control and locomotor activity in rats

    Sayaka Aizawa

    49th Japanese Neuroendocrine Society  2023.10.27 

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  • 転写因子Runx3のマウス卵胞顆粒膜細胞におけるInhbb転写制御への関与

    小島史也, 御輿真穂, 相澤清香, 竹内栄, 高橋純夫

    第46回日本比較内分泌学会大会及びシンポジウム  2022.10.28 

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  • Neuromedin U deficiency in rats does not reduce body weight or food intake

    Kyoka Yokoji, Sayaka Aizawa

    93rd The Zoological Society of Japan  2022.9.10 

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  • マウス卵巣におけるエストロゲン合成酵素アロマターゼ遺伝子Cyp19a1の発現制御

    小島史也, 藤岡竜矢, 相澤清香, 御輿真穂, 竹内栄, 高橋純夫

    日本動物学会第92回オンライン米子大会  2021.9.2 

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  • ニューロメジンU遺伝子改変ラットにおける摂食と脂肪蓄積の解析

    横木杏香, 小島史也, 竹内栄, 松山誠, 相澤清香

    日本動物学会第92回オンライン米子大会  2021.9.2 

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  • ラットにおけるニューロメジンU遺伝子欠損の摂食や肥満への影響

    横木杏果, 小島史也, 竹内栄, 松山誠, 相澤清香

    2021年度中四国地区生物系三学会合同大会香川大会  2021.6.20 

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  • ニューロメジンU(NMU)遺伝子改変ラットを用いたストレス応答機構の解析

    後藤佑紀, 横木杏香, 小島史也, 竹内栄, 松山誠, 相澤清香

    日本動物学会第91回オンライン大会  2020.9.5 

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  • The mechanism of circadian rhythm expression in the rat pituitary pars tuberalis of neuromedin U

    44th The Japan Society for Comparative Endocrinology  2019.11.10 

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  • ラット下垂体主部及び隆起部の糖タンパク質ホルモンαサブユニットの比較解析

    神之田有紗, 坂田一郎, 坂井貴文, 竹内栄, 高橋純夫, 相澤清香

    第44回日本比較内分泌学会大会及びシンポジウム  2019.11.10 

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  • ニューロメジンU遺伝子改変ラットの表現型解析

    後藤佑紀, 顧婷婷, 神之田有紗, 原田有希菜, 小島史也, 高橋純夫, 竹内栄, 松山誠, 相澤清香

    第44回日本比較内分泌学会大会  2019.11.9 

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  • マウス卵巣におけるアロマターゼ遺伝子の発現制御

    高橋純夫, 藤岡竜矢, 小島史也, 相澤清香, 御輿真穂, 竹内栄

    日本動物学会第90回大阪大会  2019.9.14 

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  • アデノシン受容体を介した下垂体隆起部ニューロメジンU発現制御の解析

    相澤清香, 顧婷婷, 神之田有紗, 坂田一郎, 坂井貴文, 小島史也, 泰山浩司, 御輿真穂, 高橋純夫, 竹内栄

    第43回日本比較内分泌学会大会  2018.11.10 

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  • アデノシンはラット下垂体隆起部のニューロメジンU mRNA発現を促進する

    相澤清香, 顧婷婷, 神之田有紗, 後藤佑紀, 塙菫, 坂田一郎, 坂井貴文, 小島史也, 泰山浩司, 御輿真穂, 高橋純夫, 竹内栄

    日本動物学会第89回札幌大会  2018.9.13 

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  • 隆起部ニューロメジンUの発現制御機構

    相沢清香, 顧婷婷, 神之田有紗, 藤岡竜矢, 坂井田初季, 塙菫, 坂田一郎, 坂井貴文, 小島史也, 泰山浩司, 御輿真穂, 竹内栄, 高橋純夫

    第42回日本比較内分泌学会大会  2017.11.18 

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  • Processing of core protein by signal peptide peptidase participates in propagation and pathogenesis of hepatitis C virus

    Sayaka Aizawa, Toru Okamoto, Takahisa Kouwaki, Takasuke Fukuhara, Kohji Moriishi, Kazuhiko Koike, Yoshiharu Matusuura

    2014.11 

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  • Processing of Core Protein by Signal Peptide Peptidase Participates in Propagation and Pathogenesis of Hepatitis C Virus

    Toru Okamoto, Sayaka Aizawa, Takahisa Kouwaki, Tatsuya Suzuki, Francesc Puig-Basagoiti, Shinya Watanabe, Takasuke Fukuhara, Kohji Moriishi, Kazuhiko Koike, Yoshiharu Matsuura

    21st International Meeting on hepatitis C virus and related viruses  2014.9 

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  • Processing of Core Protein by Signal Peptide Peptidase Participates in Propagation and Pathogenesis of Hepatitis C Virus Invited

    Toru Okamoto, Sayaka Aizawa, Takahisa Kouwaki, Tatsuya Suzuki, Francesc Puig-Basagoiti, Shinya Watanabe, Takasuke Fukuhara, Kohji Moriishi, Kazuhiko Koike, Yoshiharu Matsuura

    The Japanese Cancer Association  2014.9 

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    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

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  • Role of signal peptide peptidase in the pathogenesis of hepatitis C virus

    The Japanese Society for Virology  2014 

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    Language:Japanese   Presentation type:Oral presentation (general)  

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  • Roles of de-ubiquitinating enzymes on the propagation of HCV

    Toru Okamoto, Yukari Sugiyama, Chikako Ono, Sayaka Aizawa, Pham Duc Ngoc, Takahisa Kohwaki, Eiji Hirooka, Takasuke Fukuhara, Masahiro Yamamoto, Yoshiharu Matsuura

    International Symposium on Hepatitis C Virus and Related Viruses  2013.10 

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    Language:English   Presentation type:Oral presentation (general)  

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Awards

  • Best presentation award

    2011.8   The Japan Society for Pituitary Research   Regulation of thyroid-stimulating hormone β subunit expression by glutamate in rat pituitary pars tuberalis.

    Sayaka Aizawa

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Research Projects

  • Feeding regulatory hormone that provides feeding rhythm and prevents obesity

    2021.02 - 2022.02

    Koyanagi Zaidan 

    Sayaka Aizawa

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    Authorship:Principal investigator 

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  • The regulatory mechanism of food intake by neuromedin U

    Grant number:20K15833  2020.04 - 2023.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

    Sayaka Aizawa

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct expense: \3300000 、 Indirect expense:\990000 )

    多くの動物は摂食に概日リズムを備えているが,そのリズム形成機構の実態は不明な点が多い。申請者は以前に,摂食抑制作用をもつホルモンであるニューロメジンU(NMU)の発現が,脳下垂体隆起部において高発現し,概日リズムを示すことを明らかした。さらにNMU mRNA発現の制御には,暗期に松果体より分泌されるメラトニンが関与していることも明らかとなった。ラットは夜行性動物であり,ラットの摂食量が少ない明期にNMUの発現が高く,摂食量が多い暗期に発現が低かったことから,摂食の概日リズム形成と摂食抑制ホルモンNMUとの関連性が考えられた。そこで本研究では,摂食リズム形成に摂食抑制ホルモンNMUがどのように関わるか,特に摂食制御中枢への作用はあるのかを明らかにする。
    初年度は,CRISPR/Cas9法とラット輸卵管エレクトロポレーション法を用いて,NMU遺伝子を欠損させたNMU KOラットを作製した。その後,ヘテロ接合型同士の交配を行い,実験に使用する野生型ラットとNMU KOラットを作出した。産仔数の割合はメンデルの法則に従っており,NMU KOラットが致死ではないことが示された。NMU欠損による摂食への影響の解析としてNMU KOラットと野生型ラットの摂食量と摂食リズムを12h明期12h暗期の光環境飼育で測定した。まずは,明期,暗期それぞれの摂食量から明期/暗期の比を算出して摂食リズムの乱れを判定した。その結果は,先行研究および我々の予想に反しており,測定したいずれの週齢においても,野生型ラットとNMU KOラットで1日の摂食量に違いはみられず,また明期,暗期のそれぞれの摂食量にも違いは見られなかった。

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  • Analysis of the feeding rhythm formation mechanism by the feeding suppressing hormone Neuromedin U

    2020.04 - 2021.03

    Sanyo-hoso zaidan  Academic research grant “Academic Encouragement Award” 

    Sayaka Aizawa

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  • Elucidation of the feeding rhythm formation mechanism by the feeding suppressing hormone Neuromedin U

    2019.07 - 2020.06

    Mishima Kaiun Memorial Foundation  Academic research grants 

    Sayaka Aizawa

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  • Regulatory mechanism of neuromedin U expression in the pars tubercles

    Grant number:17K15150  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)  Grant-in-Aid for Young Scientists (B)

    AIZAWA SAYAKA

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    Grant amount:\4420000 ( Direct expense: \3400000 、 Indirect expense:\1020000 )

    Neuromedin U (NMU) shows circadian expression in the rat pars tuberalis (PT), and is known to be suppressed by melatonin. Here we examined the involvement of adenosine in the regulation of the Nmu expression. It was found that the rat PT expressed adenosine receptor A2b and an adenosine receptor agonist NECA stimulated Nmu expression in brain slice culture. An in vitro promoter assay revealed that NECA stimulated Nmu promoter activity via a cAMP response element (CRE) in the presence of adenosine receptor A2b. Furthermore, NECA increased the levels of phosphorylated CRE binding protein. These results suggest that adenosine stimulates Nmu expression by activating cAMP signaling pathway through the adenosine receptor A2b in the rat PT. This is the first report demonstrating that Nmu expression in the PT is regulated by adenosine, which acts as an intravital central metabolic signal, in addition to melatonin, which acts as an external photoperiodic environmental signal.

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  • Kallikrein 1 expression and its roles in the mouse uterus

    Grant number:17K07470  2017.04 - 2020.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Takahashi Sumio

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    Grant amount:\4940000 ( Direct expense: \3800000 、 Indirect expense:\1140000 )

    Serine protease Kallikrein1 (Klk1) was expressed in mouse endometrial epithelial cells and stromal cells. Klk1 synthesis and release from the endometrial cells were enhanced by estrogen treatment. Klk1 transcription was regulated by binding of estrogen receptor on the putative estrogen response element and/or putative AP1 sites in the promoter region. We previously reported that klk1 degraded insulin-like growth factor binding protein 3 (IGFBP3), fibronectin and collagen type IV. Elevated Klk1 production and release may enhance the IGF1 release from IGFBP3, resulting in the proliferation of endometrial cells. These findings suggest that Klk1 was involved in the proliferation of endometrial cells and the remodeling of endometrium.

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  • The mechanism of circadian expression of neuromedin U in the pars tuberalis.

    Grant number:15H06419  2015.08 - 2017.03

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    AIZAWA SAYAKA

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    Grant amount:\3250000 ( Direct expense: \2500000 、 Indirect expense:\750000 )

    The regulatory mechanism of the expression of neuromedin U (NMU) in the rat pars tuberalis. Quantitative PCR showed that melatonin receptor MT1a and adenosine receptor A2b are highly expressed in the rat pars tuberalis. In rat brain slice culture experiment, NMU mRNA expression was significantly suppressed by melatonin and significantly increased by adenosine. It is suggested that diurnal rhythm expression of NMU in the rat pars tuberalis is antagonistically regulated by adenosine and melatonin.

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Class subject in charge

  • Seminar in Molecular Endocrinology (2023academic year) Other  - その他

  • Basic Biology A (2023academic year) 1st and 2nd semester  - 金3~4

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  • Cell Biology IB (2023academic year) Fourth semester  - 火3~4

  • Basic Biology A (2022academic year) 1st and 2nd semester  - 金3~4

  • Basic Biology A1 (2022academic year) 1st semester  - 金3~4

  • Basic Biology A2 (2022academic year) Second semester  - 金3~4

  • Regulatory Biology (2022academic year) Prophase  - 金3~4

  • Endocrinology IIA (2022academic year) 1st semester  - 水1~2

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  • Seminar in Chemical Correlation and Control (2022academic year) Year-round  - その他

  • Cell Biology IB (2022academic year) Fourth semester  - 火3~4

  • Experiments in Basic Biology (2021academic year) Summer concentration  - その他

  • Experiments in Basic Biology (2021academic year) Summer concentration  - その他

  • Basic Biology A (2021academic year) 1st and 2nd semester  - 金3,金4

  • Basic Biology A1 (2021academic year) 1st semester  - 金3,金4

  • Basic Biology A2 (2021academic year) Second semester  - 金3,金4

  • Regulatory Biology (2021academic year) Prophase  - 金3,金4

  • Endocrinology (2021academic year) 1st and 2nd semester  - 水1,水2

  • Endocrinology IIA (2021academic year) 1st semester  - 水1,水2

  • Endocrinology IIB (2021academic year) Second semester  - 水1,水2

  • Endocrinology (2021academic year) Late  - その他

  • Seminar in Chemical Correlation and Control (2021academic year) Year-round  - その他

  • Cell Biology 1 (2021academic year) 3rd and 4th semester  - 火3,火4

  • Cell Biology IB (2021academic year) Fourth semester  - 火3,火4

  • Regulatory Biology (2020academic year) Prophase  - 月3,月4

  • Endocrinology (2020academic year) special  - その他

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