| Project/Area Number |
17K07075
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | mGluR7 / 射精 / 性行動 / シナプス / グルタミン酸受容体 / 脊髄切断 / 標的細胞特異的発現 / グルタミン酸 |
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| Outline of Final Research Achievements |
Metabotropic glutamate receptor subtype 7 (mGluR7) is a member of the group III mGluRs, which localized to presynaptic active zones of the 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 into the lumbosacral spinal cord inhibited PCA induced ejaculation. Immunohistochemistry revealed mGluR7-like immunoreactivity (LI) expressed in the same area where lumbar spinothalamic cells regulate the parasympathetic ejaculatory pathway. These results indicate that mGluR7 in the lumbosacral spinal cord regulates ejaculation by potentiating the excitability of parasympathetic pathway.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、不妊外来において射精障害の男性が増加している。しかしながら、アモキサピンなどの三環系抗うつ薬が逆行性射精を改善させる例を除き、射精障害に有効な薬物療法はない。
射精のメカニズムは不明な点が多い。mGluR7が射精調節に関与する神経回路を明らかにするために、免疫組織化学的解析を行い、その調節機構について考察した。mGluR7はシナプス前膜の伝達物質放出部位近傍に存在し、グルタミン酸放出の調節をしていると考えられている。今後、早漏や膣内射精障害を含めた遅漏などの射精障害の薬物ターゲットとしてのmGluR7の可能性を探索したい
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