Multi-model in vivo imaging of neuroimmune modulation in a mouse model of tauopathy

单酰基甘油脂肪酶(MAGL)通过催化内源性大麻素2-酰基甘油生成炎症反应的重要介质花生四烯酸，在终止内源性大麻素信号转导过程中发挥重要作用。为探讨MAGL抑制能否抑制Tau诱导的神经炎性改变，用单酰甘油脂肪酶(MAGL)抑制剂JZL-184对高表达病理性Tau蛋白的rTg4510小鼠进行治疗。分别于治疗前、治疗中、治疗后进行PET和MRI检查。体内成像研究表明，在脊椎病早期而不是晚期，长期抑制MAGL的功能会减缓神经退行性变的速度。此外，抑制神经炎症的作用出现在5个月，早于停止tau蓄积和挽救神经元的速度(7个月)，表明MAGL抑制可能通过其抗炎作用发挥抗tau和神经保护作用。

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.