Inhibition of mTORC2 improves brain injury in epileptic rats by promoting chaperone-mediated autophagy.

Epilepsy can seriously affect children's cognitive and behavioral development. The mechanistic target of rapamycin(mTOR) pathway plays an important role in neurodevelopment and epilepsy, but the mechanism of mechanistic target of rapamycin complex 2 (mTORC2) in epilepsy is still unclear. Here, we compared the similarities and differences of the mechanisms of action of mechanistic target of rapamycin complex 1 (mTORC1) and mTORC2 complex in the pathogenesis of epilepsy. Our research results show that the levels of apoptosis in cortical and hippocampal neurons were upregulated in epileptic rats (F = 32.15, 30.96; both P < 0.01), and epilepsy caused neuronal damage (F = 8.13, 9.43; both P < 0.01). The mTORC2-Akt pathway was activated in the cortex and hippocampus of epileptic rats. Inhibition of mTORC2 resulted in decreased levels of apoptosis and reduced neuronal damage in the cortex and hippocampus of epileptic rats. In the hippocampus, selective inhibition of mTORC2 increased lysosome-associated membrane protein 2 A (LAMP2A) protein expression compared with the control group, and the difference was statistically significant (F = 3.02, P < 0.05). Finally, we concluded that in the hippocampus, selective inhibition of mTORC2 can improve epileptic brain injury in rats by increasing chaperone-mediated autophagy (CMA) levels.