SLC1A2 mediates refractory temporal lobe epilepsy with an initial precipitating injury by targeting the glutamatergic synapse pathway

Abstract

This study aimed to identify the genes related to epilepsy and their effects on epilepsy, as well as the underlying mechanism. Using microarray analysis, differentially expressed genes (DEGs) were screened out and then used to build weighted gene coexpression networks using WGCNA. Module membership and evaluation of gene significance (GS) were adopted to detect hub genes. The DAVID online tool was used to understand the function of modules and target genes. The Licl-pilocarpine chronic rat epilepsy model was used to simulate mesial temporal lobe epilepsy with an initial precipitating injury. Hippocampal expression of the proteins solute carrier family 1 member 2 (SLC1A2), glial fibrillary acidic protein, interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), and N-methyl-d-aspartic acid receptor (NMDAR) was determined by ELISA and Western blot. Nissl staining was used to measure neuronal loss. Immunohistochemistry was performed to assess the percentage of positive cells to reflect the distribution of NMDAR1. Here, 3232 potential genes highly correlated with epilepsy were selected from the screened DEGs, among which SLC1A2 was related to brain development and its expression was significantly decreased in epilepsy patients. According to Gene Ontology and KEGG analysis, SLC1A2 mediates epilepsy through the glutamatergic synapse pathway. Tissue experiments suggested that Slc1a2 could genuinely ameliorate epilepsy through the glutamatergic synapse pathway, mitigate neuronal loss, and suppress astrocytosis and inflammatory responses. Our study suggested that low hippocampal content of SLC1A2 is a potential biomarker of epilepsy and may affect the function of neurons through the glutamatergic synapse pathway. © 2018 IUBMB Life, 71(1):213–222, 2019.