2021 Fiscal Year Final Research Report
Search for new therapeutic target molecules for fear-related disorders using a model of treatment resistance
| Project/Area Number |
19K08080
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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 | Showa Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | fear / fear extinction / sex differences / neuroimmune |
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| Outline of Final Research Achievements |
The purpose of this study is to construct the foundation for new therapeutic agents that overcome treatment resistance in fear-related disorders. In this study, we found that a peroxisome proliferator-activated receptor γ agonist rosiglitazone (i.p.) improved extinction-resistance in female mice and an immunosuppressant dexamethasone (i.p.) augmented extinction memory in the females. Additionally, the results from the present study supported our hypothesis that high immunoactivity in the dorsal hippocampus results in extinction-resistance. Furthermore, we found a possibility that TrkB in the ventral hippocampus play a sex-dependent opposite role in fear extinction, and sex differences in the role of endocannabinoid 2-AG in fear memory.
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| Free Research Field |
精神・神経薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、恐怖消去に対してPPARγの役割は調べられていなかった。本研究の成果は、恐怖消去に対するPPARγの役割に注目した研究の扉を開くものである。また、恐怖消去抵抗性が背側海馬内免疫活性に起因するという我々の仮説を支持する成果が得られた。この他にもTrkBやCBなど、恐怖記憶やその消去に性別依存的な役割を持つ分子を発見することが出来た。これらの成果は、将来的に心的外傷後ストレス障害などの恐怖関連疾患の病因解明と新規治療法の発見に繋がることが期待される。
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