Treadmill exercise improve recognition memory by TREM2 pathway to inhibit hippocampal microglial activation and neuroinflammation in Alzheimer's disease model

Alzheimer's disease-related cognition impairment is correlated with increased neuroinflammation. Studies show that physical exercises improve cognitive function and regulate neuroinflammation. However, no sufficient studies have been performed to directly observe the mechanism of exercise-related effects on microglia and neuroinflammation, in association with memory function under Alzheimer's disease. This study aims to explore the relationship of TREM2, microglia activation and neuroinflammation in the development of Alzheimer's disease, followed by investigating why physical exercises improve cognition in the Alzheimer's disease model by means of the adeno-associated virus (AAV) injection. We found that: 1) Recognition memory impairment in Aβ-induced Alzheimer's disease model was associated with the reduction in TREM2 which induced microglial activation and neuroinflammation; 2) Exercise activated the TREM2 pathway, which was necessary for inhibiting microglial activation and neuroinflammation, leading to improved recognition memory in the Alzheimer's disease model. Together, the improvement of AD-associated recognition memory by exercises is associated with up-regulation of the TREM2 pathway which promotes the phenotypic conversion of microglia and decreases the level of neuroinflammation.