| Project/Area Number |
21K15815
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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 52040:Radiological sciences-related
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| Research Institution | National Institutes for Quantum Science and Technology |
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Principal Investigator |
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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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Discontinued (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | Neuroinflammation / PET / Tau / MAGL / rTg4510 / multi-model imaging / neurodegeneration / tau / tauopathy / P2X7R |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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