title: Region-specific alterations of AMPA receptor phosphorylation and signaling pathways in the pilocarpine model of epilepsy.
abstract: Disturbances in glutamatergic transmission and signaling pathways have been associated with temporal lobe epilepsy (TLE) in humans. However, the profile of these alterations within specific regions of the hippocampus and cerebral cortex has not yet been examined. The pilocarpine model in rodents reproduces the main features of TLE in humans. The present study aims to characterize specific alterations of the glutamatergic transmission and signaling pathways in the dorsal (DH) and ventral hippocampus (VH) and temporal cortex (Ctx) of male adult Wistar rats 60 days after pilocarpine treatment (chronic period). The western blotting analyzes show a decrease of AMPA glutamate receptor subunit (GluA1)-Ser(845) phosphorylation; reduction of ERK1 and PKA activity; up-regulation of GFAP and down-regulation of the glutamate transporter EAAT2 expression in the DH. In contrast, in the VH it was observed a decrease of GluA1-Ser(831) phosphorylation and JNKp54 and PKC activity. In the Ctx, only ERK1 phosphorylation/activity decreased. The level of GluA1-Ser(845) phosphorylation and PKA activity (DH) and the level of GluA1-Ser(831) phosphorylation and PKC activity (VH) appear to be correlated, respectively. These findings suggest a differential imbalance of the signaling pathways involved in the site-specific phosphorylation of AMPA receptor in the hippocampus. Furthermore, we suggest that dorsal hippocampus is probably more susceptible to the impairment of glutamate uptake and gliose, since only this area displayed a significant decrease of EAAT2 and increment of GFAP. Taken together, our study suggests that specific neurochemical alterations take place in hippocampal sub regions. This approach may be valuable for understanding the onset of seizures and the alterations of neuronal excitability in specific regions and may help to establish therapeutic targets for treatment of this neuropathology.
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Mark William
authors.initials: MW
authors.lastname: Lopes
authors.affiliation: Programa de Pós-graduação em Farmacologia, Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Samantha Cristiane
authors.initials: SC
authors.lastname: Lopes
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Costa
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Filipe Marques
authors.initials: FM
authors.lastname: Gonçalves
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Débora Kurrle
authors.initials: DK
authors.lastname: Rieger
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Tanara Vieira
authors.initials: TV
authors.lastname: Peres
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Helena
authors.initials: H
authors.lastname: Eyng
authors.affiliation: Programa de Pós-graduação em Farmacologia, Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Rui Daniel
authors.initials: RD
authors.lastname: Prediger
authors.affiliation: Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Alexandre Paim
authors.initials: AP
authors.lastname: Diaz
authors.affiliation: Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Jean Costa
authors.initials: JC
authors.lastname: Nunes
authors.affiliation: Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Centro de Neurociências Aplicadas (CeNAp), Hospital Universitário (HU), Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Departamento de Clínica Médica, Hospital Universitário (HU), Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors.forename: Roger
authors.initials: R
authors.lastname: Walz
authors.affiliation: Programa de Pós-graduação em Bioquímica, Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil; Programa de Pós-graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. Electronic address: rbleal@gmail.com.
authors.forename: Rodrigo Bainy
authors.initials: RB
authors.lastname: Leal
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D010862:Pilocarpine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018091:Receptors, AMPA; D010862:Pilocarpine
keywords: AMPA receptor phosphorylation; Epilepsy; Hippocampus; Pilocarpine; Signaling pathways