Electroacupuncture Promotes Autophagy by Regulating the AKT/mTOR Signaling Pathway in Temporal Lobe Epilepsy

Abstract

Temporal lobe epilepsy (TLE) is a complex neurological disease, and its occurrence and development are closely related to the autophagy signaling pathway. However, the mechanism by which electroacupuncture (EA) affects the regulation of autophagy has not been fully elucidated. TLE gene chip dataset GSE27166 and data from rats without epilepsy (n = 6) and rats with epilepsy (n = 6) were downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) in the TLE and control groups were identified with the online tool GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to analyse the functional and pathway enrichment of genes in the most important modules. A rat model of TLE induced by lithium-pilocarpine treatment was established. EA treatment at DU20 and DU14 in TLE rats was performed for 2 weeks. Neuronal regeneration was determined using immunofluorescence staining. The protein levels of AKT/mTOR signaling pathway and autophagy markers were detected through western blotting and immunohistochemistry. This study identified 1837 DEGs, including 798 upregulated genes and 1039 downregulated genes. GO enrichment and KEGG analyses were performed on DEGs and revealed functional enrichment mainly in the mTOR signaling pathway and autophagy-animal. Furthermore, the number of mature neurons was significantly increased upon coexpressing BrdU/NeuN in TLE rats treated with EA. Western blotting and immunohistochemistry results showed significantly decreased levels of the phosphorylated-AKT and p-mTOR in the hippocampal CA3 and DG regions of TLE rats with EA treatment. And increased p-ULK1/ULK1, LC3-II/LC3-I and p62 levels in TLE rats with EA stimulation. Therefore, this study suggested that EA promoted autophagy in hippocampal neurons during the onset of epilepsy by regulating the AKT/mTOR signaling pathway to treat epilepsy.

Keywords: Electroacupuncture; Hippocampus; Neurology; Temporal lobe epilepsy; mTOR signaling pathway.