title: GSK-3β may be involved in hippocampal mossy fiber sprouting in the pentylenetetrazole-kindling model.
abstract: Mossy fiber sprouting (MFS) is a pathological phenomenon that is commonly observed in temporal lobe epilepsy (TLE). However, the molecular mechanisms underlying MFS remain unclear. It has been demonstrated that the tau protein is important in the progression of MFS by the regulation of microtubule dynamics and axonal transport, with all of these functions of tau modulated by its site-specific phosphorylation. Glycogen synthase kinase-3β (GSK-3β) is an active kinase that regulates the phosphorylation of tau protein. Therefore, it was hypothesized that GSK-3β contributes to MFS by phosphorylating tau protein. The aim of the present study was to determine the expression and activity of GSK-3β at different regions in the rat hippocampus during the pentylenetetrazole (PTZ)-kindling process in order to demonstrate the possible correlation with MFS, and to investigate the involvement of GSK-3β in epileptogenesis. Male Sprague-Dawley rats (n=180) were randomly divided into the control and PTZ-treated groups. The chronic epileptic model was established by intraperitoneal injection of PTZ and the hippocampus was observed for the presence of MFS using Timm staining. GSK-3β mRNA, protein and activity were analyzed in various regions of the hippocampus using in situ hybridization, immunohistochemistry and immunoprecipitation followed by a kinase assay and liquid scintillation counting, respectively. MFS was observed prior to kindling and an increased distribution of Timm granules were observed in the CA3 region of the PTZ-treated rats; however, this was not demonstrated in the supragranular layer of the dentate gyrus. The expression of GSK-3β mRNA and protein, as well as the GSK-3β activity, increased significantly from 3 days to 4 weeks in the PTZ group, and this was correlated with the progression of MFS in the CA3 area. In addition, it was demonstrated that MFS did not result from TLE. GSK-3β may therefore be involved in the progression of MFS and is important in epileptogenesis. An understanding of the molecular mechanisms underlying MFS may lead to the identification of a novel therapeutic target to limit epileptogenesis.
authors.affiliation: Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Wen-Jiao
authors.initials: WJ
authors.lastname: Huang
authors.forename: Fa-Fa
authors.initials: FF
authors.lastname: Tian
authors.forename: Jin-Mei
authors.initials: JM
authors.lastname: Chen
authors.forename: Ting-Hui
authors.initials: TH
authors.lastname: Guo
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Ma
authors.forename: Jia
authors.initials: J
authors.lastname: Fang
authors.forename: Jing
authors.initials: J
authors.lastname: Dang
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Song
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003292:Convulsants / Q000633:toxicity*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D007696:Kindling, Neurologic / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010433:Pentylenetetrazole / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: D003292:Convulsants; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D010433:Pentylenetetrazole