| Project/Area Number |
21K07532
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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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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Okayama University of Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
橋川 直也 岡山理科大学, 理学部, 准教授 (60434982)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | CGRP / マウス / エピジェネティクス / 転写調節因子 / 恐怖記憶 / 鼻腔内投与 / Npas4 / PTSD |
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| Outline of Research at the Start |
CGRPは痛みを感じる時に神経から遊離されるペプチドで、申請者はこれまでCGRPを外的に投与すると抗うつ作用を示すことを報告してきた。しかしながら恐怖記憶においての作用は未だ不明な点が多い。
本研究において、マウスにCGRPを投与することで恐怖記憶に対する影響を明らかにし、特に転写因子のNpas4を介したエピジェネティックな調節機構を明らかにする。
さらにヒトでの臨床試験を視野に入れたCGRPの投与法を確立させ、新たな心的外傷後ストレス障害（PTSD）治療薬ターゲット候補となることを目指す。
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| Outline of Final Research Achievements |
We discovered that administering CGRP to mice that had experienced a traumatic event resulted in the mice not recalling the fearful memory. CGRP is one of the neurotransmitters contained in pain-transmitting nerves and exhibits vasodilatory effects. Although CGRP is also abundantly expressed in the brain, its relationship with memory was not previously clear. We analyzed the effects of CGRP administration on spatial memory, short-term memory, and fear memory in mice, and found that CGRP has the effect of alleviating fear memory. This effect of CGRP was found to be due to an increase in the expression of the transcriptional regulator Npas4. Furthermore, it was revealed that the increase in Npas4 induced by CGRP occurs through epigenetic regulatory mechanisms, which are forms of acquired gene expression control. Epigenetics is attracting attention as a drug discovery target, and the results of this study suggest that CGRP could be a potential new therapeutic target for PTSD.
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| Academic Significance and Societal Importance of the Research Achievements |
エピジェネティクスは創薬標的としての注目を集めており、本研究成果はCGRPが新たな心的外傷後ストレス(PTSD)の新たな治療ターゲットになり得ることを示唆しています。
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