研究課題/領域番号 |
21K15815
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研究種目 |
若手研究
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配分区分 | 基金 |
審査区分 |
小区分52040:放射線科学関連
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研究機関 | 国立研究開発法人量子科学技術研究開発機構 |
研究代表者 |
Zhou Xiaoyun 国立研究開発法人量子科学技術研究開発機構, 量子医科学研究所 脳機能イメージング研究部, 研究員 (40834099)
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研究期間 (年度) |
2021-04-01 – 2023-03-31
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研究課題ステータス |
中途終了 (2022年度)
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配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2022年度: 1,820千円 (直接経費: 1,400千円、間接経費: 420千円)
2021年度: 2,860千円 (直接経費: 2,200千円、間接経費: 660千円)
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キーワード | Neuroinflammation / PET / Tau / MAGL / rTg4510 / multi-model imaging / neurodegeneration / tau / tauopathy / P2X7R |
研究開始時の研究の概要 |
We will employ in vivo imaging techniques, including PET and MRI, and in vitro biochemical strategies to assess the effects of inhibition of MAGL and P2X7R on proinflammatory microgliosis, protein aggregation, demyelination, and neurodegeneration during the course of tauopathy in rTg4510 mice.
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研究実績の概要 |
Monoacylglycerol lipase (MAGL) plays an important role in terminating endocannabinoid signaling by catalyzing endocannabinoid 2-acylglycerol to form arachidonic acid, an important mediator of inflammatory responses. To explore whether MAGL inhibition could limit pathological Tau-induced neuroinflammatory changes, rTg4510 mice with overexpressing pathological Tau protein have been treated with JZL-184, an inhibitor of monoacylglycerol lipase (MAGL). PET and MRI were carried out before, during, and after the treatment. The in vivo imaging studies revealed that chronic inhibition of the function of MAGL at an early but not late stage of tauopathy decelerated neurodegeneration. Furthermore, the effect of the treatment on constraining neuroinflammation occurred at five months, early than halting the rate of tau accumulation and rescuing neurons (at 7 months), indicating that MAGL inhibition may exert anti-tau and neuroprotective functions via its anti-inflammatory effects.
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