PMID- 30360015 OWN - NLM STAT- MEDLINE DCOM- 20200113 LR - 20200204 IS - 1521-6551 (Electronic) IS - 1521-6543 (Linking) VI - 71 IP - 2 DP - 2019 Feb TI - SLC1A2 mediates refractory temporal lobe epilepsy with an initial precipitating injury by targeting the glutamatergic synapse pathway. PG - 213-222 LID - 10.1002/iub.1956 [doi] AB - 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-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), 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. (c) 2018 IUBMB Life, 71(1):213-222, 2019. CI - (c) 2018 International Union of Biochemistry and Molecular Biology. FAU - Zhang, Yinian AU - Zhang Y AUID- ORCID: 0000-0001-5377-0381 AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. FAU - Dong, Huateng AU - Dong H AD - Department of Pediatric Neurology, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, 730050, Gansu, China. FAU - Duan, Lei AU - Duan L AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. FAU - Yuan, Guoqiang AU - Yuan G AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. FAU - Liang, Wentao AU - Liang W AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. FAU - Li, Qiao AU - Li Q AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. FAU - Zhang, Xinding AU - Zhang X AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. FAU - Pan, Yawen AU - Pan Y AD - Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu, China. AD - Institute of Neurology, Lanzhou University, Lanzhou, 730030, Gansu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181025 PL - England TA - IUBMB Life JT - IUBMB life JID - 100888706 RN - 0 (Biomarkers) RN - 0 (Excitatory Amino Acid Transporter 2) RN - 0 (GFAP protein, rat) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (IL1B protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (NMDA receptor A1) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Slc1a2 protein, rat) RN - 0 (Tumor Necrosis Factor-alpha) RN - 01MI4Q9DI3 (Pilocarpine) RN - G4962QA067 (Lithium Chloride) SB - IM MH - Animals MH - Astrocytes/metabolism/pathology MH - Biomarkers/metabolism MH - Cell Death MH - Epilepsy, Temporal Lobe/chemically induced/*genetics/metabolism/physiopathology MH - Excitatory Amino Acid Transporter 2/*genetics/metabolism MH - Gene Expression Regulation MH - Glial Fibrillary Acidic Protein/genetics/metabolism MH - Hippocampus/metabolism/physiopathology MH - Humans MH - Interleukin-1beta/genetics/metabolism MH - Lithium Chloride/administration & dosage MH - Male MH - Neurons/*metabolism/pathology MH - Pilocarpine/administration & dosage MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*genetics/metabolism MH - Synapses/*metabolism/pathology MH - Synaptic Transmission MH - Tumor Necrosis Factor-alpha/genetics/metabolism OTO - NOTNLM OT - SLC1A2 OT - WGCNA-analysis OT - epilepsy OT - glutamatergic synapse pathway OT - neurons EDAT- 2018/10/26 06:00 MHDA- 2020/01/14 06:00 CRDT- 2018/10/26 06:00 PHST- 2018/07/03 00:00 [received] PHST- 2018/08/30 00:00 [revised] PHST- 2018/09/08 00:00 [accepted] PHST- 2018/10/26 06:00 [pubmed] PHST- 2020/01/14 06:00 [medline] PHST- 2018/10/26 06:00 [entrez] AID - 10.1002/iub.1956 [doi] PST - ppublish SO - IUBMB Life. 2019 Feb;71(2):213-222. doi: 10.1002/iub.1956. Epub 2018 Oct 25.