Cerebral protection by electroacupuncture pretreatment: a mechanism via autophagy involving the mTORC1 pathway

On the basis of our previous studies that Electroacupuncture (EA) pretreatment exerts protection on brain by inhibiting the autophagy, but the mechanism how it to modulate the autophagy is only poorly understood. We aimed to identify the effect of EA pretreatment on mTOR pathway. We mainly evaluated the effect of EA on the autophagic upstream protein mammalian target rapamycin (mTOR), the AMP-activated protein kinase (AMPK), the protein kinase B (AKT) and the two mTOR complex (regulatory associated protein of TOR, mTORC1) and rapamycin-insensitive companion of mTOR, mTORC2). First, EA at the acupoint "baihui (GV20)" 30 min/day, for five consecutive days before the ischemia reperfusion significantly increased the level of the phosphorylation of mTOR (p-mTOR) especially the site of 2481, and inhibited the expression of autophagy. While the specific inhibitor of mTOR Rampaycin inversed the inhibition of EA on p-mTOR, and upregulated the expression of autophagy, as a result, weaken the protection of EA on brain ischemia/reperfusion (IR). In addition, EA obviously raised the mTOR complex Raptor, but almostly have no effect on the other mTOR complex (Rictor). Second, EA increased the level of phosphorylation of AKT (p-AKT), and the p-AKT and p-mTOR (2481) were positively correlated (r = 0.897, P < 0.05). This study demonstrated that EA pretreatment of Baihui leads to the phosphorylation of AKT, thereby promoting mTOR phosphorylation and ultimately inhibiting autophagy and protecting the brain.