title: Downregulation of gephyrin in temporal lobe epilepsy neurons in humans and a rat model.
abstract: Gephyrin, which is a postsynaptic scaffolding protein participated in clustering GABA(A) receptors at inhibitory synapses, has been reported to be involved in temporal lobe epilepsy (TLE) recently. Here, we investigate gephyrin protein expression in the temporal lobe epileptic foci in epileptic patients and experimental animals in order to explore the probable relationship between gephyrin expression and TLE. Using immunohistochemistry, immunofluorescence, and western blot analysis, gephyrin expression was examined in 30 human temporal neocortex samples from patients who underwent surgery to treat drug-refractory TLE and 10 histological normal temporal neocortex from the controls. Meanwhile, we investigated the gephyrin expression in the hippocampus and adjacent neocortex from experimental rats on 24 h, 48 h, 1 week, 2 weeks, 1 month, and 2 months postseizure and from control rats. Gephyrin protein was mainly expressed in the membrane and cytoplasm of neurons in temporal lobe epileptic foci in humans and experimental rats. Gephyrin expression was significantly lower in the temporal neocortex of TLE patients compared to the controls. In experimental rats, the expression of gephyrin in temporal lobe was downregulated in epileptic groups compared to the control group. Gephyrin expression gradually decreased during the acute period and the latent period, but then began to increase below the levels seen in controls during the chronic phase. Our findings suggest that gephyrin may be involved in the development of TLE.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.forename: Huan
authors.initials: H
authors.lastname: Yin
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Pan
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Xi
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiao
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Sheng-Nian
authors.initials: SN
authors.lastname: Zhou
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008875:Middle Aged; D019579:Neocortex / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013702:Temporal Lobe / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C073441:gephyrin