Elucidation of pathophysiological implications of interneuron degeneration in frontotemporal dementia
| Project/Area Number |
17K08280
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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 |
Biological pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
Tsuiji Hitomi 名古屋市立大学, 医薬学総合研究院(薬学), 講師 (40455358)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 前頭側頭葉変性症 / 抑制性介在ニューロン / 筋萎縮性側索硬化症 / TDP-43 / 加齢 / 神経変性 / 神経変性疾患 / 凝集 / パルブアルブミン / RNA結合タンパク質 |
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| Outline of Final Research Achievements |
TDP-43 is an RNA-binding protein important for many aspects of RNA metabolism. Abnormal accumulation of TDP-43 in the cytoplasm of affected neurons is a pathological hallmark of the neurodegenerative diseases frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Here, we analyse age-dependent changes in TDP-43 transgenic mice that displayed impaired memory. We found the accumulation of abundant poly-ubiquitinated protein aggregates in the hippocampus of aged TDP-43 transgenic mice. Intriguingly, the aggregates contained some interneuron-specific proteins such as parvalbumin and calretinin, suggesting that GABAergic interneurons were degenerated in these mice. The abundance of aggregates significantly increased with age and with the overexpression of TDP-43.Our results indicate that the interneuron degeneration occurs upon aging, and TDP-43 accelerates age-dependent neuronal degeneration, which may be related to the impaired memory of TDP-43 transgenic mice.
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| Academic Significance and Societal Importance of the Research Achievements |
加齢に伴って抑制性介在ニューロンが変性し死んでいくこと、認知症の一つである前頭側頭葉変性症FTDのモデルマウスではその変性死が加速することを見出した。これは、認知症の初期症状として知られているニューロンの過剰な興奮を説できる可能性がある。
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Report
(4 results)
Research Products
(5 results)
