Changes in GABAergic inputs to GnRH neurons causing stress induced reproductive dysfunction
Project/Area Number |
16K08523
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Environmental physiology(including physical medicine and nutritional physiology)
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
Watanabe Miho 浜松医科大学, 医学部, 助教 (10399321)
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Project Period (FY) |
2016-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | GABA / GnRHニューロン / KCC2 / 生殖 / 視床下部 / クロライド / NKCC1 / 神経内分泌 / ストレス / 神経内分泌学 |
Outline of Final Research Achievements |
The GnRH neurosecretory system constitutes the final common pathway in the neuroendocrine control of reproduction. GABA acts excitatory on GnRH neurons. Overexpression of KCC2 inhibited calcium oscillations in GnRH neurons. Stress may cause the disruption of intracellular chloride homeostasis in GnRH neurons, thereby lead to reproductive dysfunction.
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Academic Significance and Societal Importance of the Research Achievements |
本研究ではGnRHニューロンの機能不全による生殖機能低下のメカニズムの一端を明らかにすることができた。ストレスや栄養状態の低下による体重減少などにより、視床下部-下垂体の機能が低下し、無月経や無排卵になる中枢性排卵障害の原因の一つにGnRHニューロンの機能不全が考えられる。ヒトのGnRHニューロンへもGABA入力があることがわかっており、細胞内クロライド濃度維持機構の破綻とGnRHニューロンの機能不全との関連性を示唆した本研究の成果は無排卵や不妊症などの治療、新たな治療薬開発への貢献が考えられる。
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Report
(5 results)
Research Products
(36 results)
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[Journal Article] Time-controllable Nkcc1 knockdown replicates reversible hearing loss in postnatal mice.2017
Author(s)
Watabe T, Xu M, Watanabe M, Nabekura J, Higuchi T, Hori K, Sato MP, Nin F, Hibino H, Ogawa K, Masuda M, Tanaka KF
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Journal Title
Science Reports
Volume: 7
Issue: 1
Pages: 13605-14007
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Impaired neuronal KCC2 function by biallelic SLC12A5 mutations in migrating focal seizures and severe developmental delay.2016
Author(s)
Saitsu H, Watanabe M, Akita T, Ohba C, Sugai K, Ong WP, Shiraishi H, Yuasa S, Matsumoto H, Beng KT, Saitoh S, Miyatake S, Nakashima M, Miyake N, Kato M, Fukuda A. and Matsumoto N.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 30072-30072
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] A novel excitatory GABAergic input from the arcuate nucleus to the median eminence involved in CRH release2016
Author(s)
Fukuda A, Kakizawa K, Watanabe M, Mutoh H, Okawa Y, Yamashita M, Yanagawa Y, Itoi K, Suda T, Oki Y
Organizer
The 13th Korea-Japan Joint Symposium of Brain Sciences, and Cardiac and Smooth Muscle Sciences
Place of Presentation
Saga
Year and Date
2016-08-22
Related Report
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