2020 Fiscal Year Final Research Report
Pathophysiological significance of prefrontal telomere shortening in depression
| Project/Area Number |
19K17095
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | うつ病 / テロメア / テロメラーゼ |
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| Outline of Final Research Achievements |
The telomere is an essential structure to stabilize chromosomes throughout the cell cycle. Recently, it was reported that telomere length was abnormally shortened in psychiatric disorders such as depression and PTSD. In this study, we investigated the mechanism of telomere length shortening in depression using the animal model of depression (3wFS), exposed to aversive stress (foot shock: FS) at 3 weeks-age. We revealed that telomere length was shortened in the medial prefrontal cortex and hippocampus in the 3wFS group. Moreover, we elucidated the down-expression of telomerase reverse transcriptase (TERT) protein in the hippocampus. In the immunohistochemical experiments, we revealed that TERT protein in the hippocampus was detected in mature neurons but not neural stem cells.
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| Free Research Field |
神経薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
これまでうつ病の病態については、モノアミン仮説やダウンレギュレーション仮説など抗うつ薬の薬理作用機序から逆行的に導かれることが主流であった。近年よく考察される神経新生仮説についても、抗うつ薬による神経由来成長因子 (BDNF)の増加と神経新生亢進の所見が決め手であり、本質的には同一の考え方である。そのため病態仮説に基づいたこれまでのうつ病の創薬は、モノアミン神経系に作用するものに限られていた。本研究は既存の抗うつ薬やモノアミン系に捉われない、うつ病研究の新しい切り口や創薬ターゲットを示すものであり、うつ病の新規治療戦略を開拓する上で一助となることが期待される。
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