2022 Fiscal Year Final Research Report
Elucidation of the mechanism of impaired fear memory extinction due to the impairment of histone methylation and development of novel treatment for PTSD
Project/Area Number |
20K16649
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 52030:Psychiatry-related
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Research Institution | Hiroshima University |
Principal Investigator |
Kataoka Tsutomu 広島大学, 医系科学研究科(医), 専門研究員 (10868805)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | PTSD / 動物モデル / エピジェネティクス / 新規治療薬 |
Outline of Final Research Achievements |
The purpose of this study was to elucidate the mechanism of hippocampal brain-derived neurotrophic factor (BDNF) reduction associated with impaired fear memory extinction in SPS rats, a model of PTSD. Two hours after fear memory extinction training, BDNF mRNA expression was significantly decreased in SPS rats, and the decrease might be due to the increase in the H3K9 dimethylation at BDNF promoter IV region. In addition, administration of a histone methyltransferase inhibitor reversed the decrease in BDNF expression after extinction training in SPS rats and improved the impairment of fear memory extinction. These results suggest that the regulation of BDNF gene expression mediated by H3K9 methylation in the hippocampus is involved in the impairment of fear memory extinction in SPS rats.
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Free Research Field |
精神神経医科学
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、PTSDの病態に関与するH3K9メチル化障害を証明するとともに、ヒストンメチル化酵素阻害薬の投与がPTSDの恐怖記憶の消去障害の治療法となり得ることを示した。これは、これまでのヒストン・アセチル化の亢進を標的としたヒストン脱アセチル化酵素阻害薬によるPTSD治療薬の開発に対して、新たなエピジェネティック作動薬の治療薬としての可能性を示したものである。
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