title: Lentiviral Vector-Induced Overexpression of RGMa in the Hippocampus Suppresses Seizures and Mossy Fiber Sprouting.
abstract: Repulsive guidance molecule a (RGMa) is a membrane-bound protein that inhibits axon outgrowth in the central nervous system. Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent spontaneous seizures. To explore the role of RGMa in epilepsy, we investigated the expression of RGMa in patients with TLE, pilocarpine-induced rat model, and pentylenetetrazol kindling model of epilepsy, and then we performed behavioral, histological, and electrophysiological analysis by lentivirus-mediated overexpression of RGMa in the hippocampus of animal model. We found that RGMa was significantly decreased in TLE patients and in experimental rats from 6 h to 60 days after pilocarpine-induced seizures. In two types of epileptic animal models, pilocarpine-induced model and pentylenetetrazol kindling model, overexpression of RGMa in the hippocampus of rats exerted seizure-suppressant effects. The reduced spontaneous seizures were accompanied by attenuation of hippocampal mossy fiber sprouting. In addition, overexpression of RGMa inhibited hyperexcitability of hippocampal neurons via suppressing NMDAR-mediated currents in Mg2+-free-induced organotypic slice model. Collectively, these results demonstrate that overexpression of RGMa could be an alternative strategy for epilepsy therapy.
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.|Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
authors: Ling
authors: L
authors: Chen
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Baobing
authors: B
authors: Gao
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Min
authors: M
authors: Fang
authors: Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, 453100, Henan Province, China.
authors: Jie
authors: J
authors: Li
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Xiujuan
authors: X
authors: Mi
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Xin
authors: X
authors: Xu
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Wei
authors: W
authors: Wang
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Juan
authors: J
authors: Gu
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Bo
authors: B
authors: Tang
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Yanke
authors: Y
authors: Zhang
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Zhihua
authors: Z
authors: Wang
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Ao
authors: A
authors: Zhan
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China.
authors: Guojun
authors: G
authors: Chen
authors: Department of Neurology, Chongqing Key Laboratory of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 You Yi Road, Chongqing, 400016, China. xfyp@163.com.
authors: Xuefeng
authors: X
authors: Wang
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; C522183:RGMA protein, human
keywords: Lentivirus; Mossy fiber sprouting; RGMa; Temporal lobe epilepsy