FAM134B Attenuates Seizure-Induced Apoptosis and Endoplasmic Reticulum Stress in Hippocampal Neurons by Promoting Autophagy.

Abstract

Autophagy plays a critical role in epileptic neuronal injury, and recent studies have demonstrated that FAM134B plays an important role in regulating autophagy. However, the effect of FAM134B on epileptic neuronal injury remains unclear. In this study, we investigated the role of FAM134B in neuronal apoptosis and endoplasmic reticulum (ER) stress using the hippocampal neuronal culture model of acquired epilepsy (AE) in vitro. We found that in this model, the level of autophagy significantly increased, indicated by an elevated LC3-II/LC3-I ratio. FAM134B overexpression using lentiviral vectors enhanced autophagy, whereas FAM134B downregulation using lentiviral vectors impaired this process. In addition, the ER Ca2+ concentration was decreased and the intracellular level of reactive oxygen species was increased in this model. FAM134B overexpression was sufficient to reverse these changes. Moreover, FAM134B overexpression attenuated ER stress as shown by a decrease in the expression of C/-EBP homologous protein and glucose-regulated protein 78, and neuronal apoptosis induced by seizure, while FAM134B downregulation caused the opposite effects. Further, pre-treatment with the selective autophagy inhibitor 3-methyladenine abolished the effects of FAM134B on ER stress and neuronal apoptosis. Altogether, we demonstrate that FAM134B is an important regulator of AE-induced ER stress and neuronal apoptosis by controlling autophagy function.