Treadmill Exercise Prevents Cognitive Impairments in Adolescent Intermittent Ethanol Rats by Reducing the Excessive Activation of Microglia Cell in the Hippocampus

Abstract

The excessive activation of microglia cell induced by adolescent intermittent ethanol (AIE) leads to neuroinflammation in the hippocampus. The endocannabinoid system plays a key role in the modulation of microglia activation. Accumulating evidence suggests that regular exercise improves learning and memory deficits in AIE models. The purpose of this study was to explore the effects of treadmill exercise intervention on the cognitive performance, activation of microglia cells and the expression of monoacylglycerol lipase (MAGL), cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R) in the hippocampus of AIE rats. Here, we show that AIE rats exhibited cognitive impairments, whereas the treadmill exercise improves the cognitive performance in AIE rats. In order to explore the possible mechanisms for the exercise-induced attenuation of cognitive disorder, we examined the neuroinflammation in the hippocampus. We found that treadmill exercise led to the decrease in the level of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and the increase in the level of anti-inflammatory cytokine (IL-10). In addition, we found that treadmill exercise reduced the excessive activation of the microglia cell in the hippocampus of AIE rats. Finally, we found that AIE led to a decrease in the expression of CB1R and CB2R in the hippocampus; however, the treadmill exercise further decreased the expression of CB2R in the hippocampus of AIE rats. Our results suggest that treadmill exercise attenuates AIE-induced neuroinflammation and the excessive activation of hippocampus microglial cells, which may contribute to the exercise-induced improvement of cognitive performance in AIE rats.