2021 Fiscal Year Research-status Report
Multi-model in vivo imaging of neuroimmune modulation in a mouse model of tauopathy
Project/Area Number |
21K15815
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Research Institution | National Institutes for Quantum Science and Technology |
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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Keywords | Neuroinflammation / PET / multi-model imaging / MAGL / neurodegeneration / tau |
Outline of Annual Research Achievements |
rTg4510 mice, a mouse model of tauopathy have been treated with an inhibitor of monoacylglycerol lipase (MAGL). PET and MRI were carried out before, during the procedure, and after the treatment. The in vivo imaging studies revealed that chronic inhibition of the activity of MAGL at an early but not late stage of tauopathy decelerated neurodegeneration. Furthermore, the effect of the treatment on constraining neuroinflammation occurred early than halting the rate of tau accumulation and rescuing neurons, indicating that MAGL inhibition may exert anti-tau and neuroprotective functions via its anti-inflammatory effects.
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Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We have successfully answered our research questions regarding a potential new biomarker for the treatment of neuroinflammation-associated neurodegenerative disorders, the mechanisms of action, and the optimal regimen. Furthermore, our multi-model in vivo imaging strategy allows us to discover new therapeutic targets, evaluate new CNS drugs, and explore underlying biochemical mechanisms. Our new findings attracted attention from a pharmaceutical company, as a result, a collaborative study was recently started to evaluate a novel MAGL-based drug.
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Strategy for Future Research Activity |
We will continue to collaborate with the pharmaceutical company for evaluating the new drug. Furthermore, we will investigate the therapeutic effects of P2X7 receptor inhibition. As our pervious study qualified the utility of a radiotracer for the imaging of this receptor, the future experiment will apply multi-model imaging strategy to evaluate the therapeutic efficacy of P2X7 receptor inhibition via quantification of receptor density, the burden of tau deposition, the degree of neuroinflammation, demyelination, and brain volume loss in a mouse model of tauopathy. The study will hopefully provide new insights into the mechanisms underlying the detrimental effect of P2X7 receptor activation on neuroinflammation and neurodegeneration.
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Causes of Carryover |
We have saved money on purchasing experimental materials such as antibodies and radiotracers last year. This year, we will expand our research to evaluate more drug candidates applying multiple strategies, including several longitudinal experiments, multi-model imaging, and ex vivo biochemical assays. The money left from the last year will be used in new studies. The total amount of money will be allocated to 1) experimental materials including experimental animals, chemical syntheses, chemicals, ELISA kits, and antibodies; 2) publication fees; 3) travelling expenses.
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