Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats.

Abstract

Status epilepticus (SE) is a neurological disorder associated with high morbidity and mortality rates, and is often difficult to treat. Moreover, the underlying mechanism of SE remains unknown. The lithium-pilocarpine model is a validated animal model that can reproduce the main clinical and neuropathological features of SE. In the present study, this SE model was utilized and SE was successfully established in rats, as determined by the corresponding epileptic electroencephalogram. Histology, immunohistochemistry, western blot analysis and co-immunoprecipitation were used to detect the phosphorylation (p-) of AKT substrate of 40 kDa (PRAS40), the combination of p-PRAS40 and 14-3-3 protein and the activation of the PI3K/mTOR signaling pathway in SE. In addition, the present study analyzed the dynamics of the expression of autophagy-associated factors in the hippocampus after SE induction, and the influence of suppressing the p- of PRAS40 on the autophagy process was detected in the pathogenesis of SE. The results indicated that increased p-PRAS40 expression could activate the mTOR pathway to decrease the level of autophagy. However, inhibition of the mTOR signaling pathway promoted autophagy flux. These results may provide further understanding of p-PRAS40 functions in SE.