Neuropsychiatric Disease and Treatment (Oct 2020)
LncRNA MEG3 Reduces Hippocampal Neuron Apoptosis via the PI3K/AKT/mTOR Pathway in a Rat Model of Temporal Lobe Epilepsy
Abstract
Hongyan Zhang,1 Jiuyun Tao,2 ShuXia Zhang,3 XinXin Lv4 1Department of Pediatrics, The First People’s Hospital of Jinan, Jinan, Shandong 250011, People’s Republic of China; 2Department of Surgery 1, Chiping County People’s Hospital, Liaocheng, Shandong 252100, People’s Republic of China; 3Department of Obstetrics, Zhangqiu People’s Hospital of Jinan City, Jinan, Shandong 250200, People’s Republic of China; 4Department of Pediatrics, Jining First People’s Hospital, Jining, Shandong 272000, People’s Republic of ChinaCorrespondence: XinXin LvDepartment of Pediatrics, Jining First People’s Hospital, No. 6 Jiankang Road, Jining, Shandong 272000, People’s Republic of ChinaEmail [email protected]: Temporal lobe epilepsy (TLE) is a common neurological disorder, which is characterized by recurrent spontaneous seizures. Exploring the mechanisms of epileptogenesis has been considered as a priority. The aim of this study is to investigate the effects of LncRNA MEG3 in spontaneous recurrent epileptiform discharges (SREDs) and rats with TLE.Methods: Rat model of TLE was produced by intraperitoneal injection of lithium chloride and pilocarpine. Rat hippocampal neuronal model of SREDs was established by Mg2+-free treatment. MEG3 was overexpressed by transfection of AAV-MEG3 in TLE and SREDs model. The expression of MEG3, interleukin-1β (IL-1β), interleukin-6 (IL-6) and recombinant human tumor necrosis factor-alpha (TNF-α) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected by corresponding kit. The apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase transfer‑mediated dUTP nick end‑labeling (TUNEL) assay and flow cytometry. The expression of proteins related to apoptosis (Caspase-3, Bax, and Bcl-2) and the PI3K/AKT/mTOR pathway was detected by Western blot.Results: MEG3 expression was downregulated in SREDs and rats with TLE. Overexpression of MEG3 reduced the expression of IL-1β, IL-6, and TNF-α, MDA content, apoptosis rate of hippocampal neuron, increased SOD activity, and inhibited the PI3K/AKT/mTOR pathway in rats with TLE. In addition, overexpression of MEG3 enhanced cell viability and inhibited apoptosis through the activation of the PI3K/AKT/mTOR pathway in SREDs.Conclusion: MEG3 reduced proinflammatory cytokines, oxidative stress, and apoptosis rate of hippocampal neuron and enhanced cell viability through the activation of the PI3K/AKT/mTOR pathway in SREDs and rats with TLE. Our findings may contribute to find a new therapeutic target for the treatment of epilepsy.Keywords: LncRNA MEG3, temporal lobe epilepsy, PI3K/AKT/mTOR pathway, apoptosis, inflammatory cytokines
