title: AMPA receptor properties are modulated in the early stages following pilocarpine-induced status epilepticus.
abstract: Glutamate over-activation and the consequent neuronal excitotoxicity have been identified as crucial players in brain dysfunctions such as status epilepticus (SE). Owing to the central function of 2-amino-3-(hydroxyl-5-methylisoxazole-4-yl) propionic acid receptors (AMPARs) in fast excitatory neurotransmission, these receptors have been recognized to play a prominent role in the development and generation of epileptic seizure. This study was undertaken to investigate both the early changes that affect glutamatergic neurons in the rat cerebral cortex and hippocampus and the level and channel properties of AMPARs in response to SE. The results obtained after 3 h of pilocarpine (PILO)-induced SE showed a disorganization of glutamatergic neurons in the CA3 and a thinner neuronal cell layer in the dentate gyrus (DG) region as compared with controls. A significant increase in AMPAR GluA2 protein expression, a decrease in GluA1, GluA3, and GluA4 expression, and a reduction in the phosphorylation of Ser831-GluA1 and Ser880-GluA2 were also observed. In addition, we report a downregulation of R/G editing levels and of Flip splicing isoforms, with a prominent effect on the hippocampus of PILO-treated rats. Our results suggest the presence of an attenuation of AMPARs' post-synaptic excitatory response to glutamate after PILO treatment, thus conferring neuronal protection from the excitotoxic conditions observed in the SE. This study suggests a role for AMPARs in alterations of the glutamatergic pathway during the onset and early progression of epilepsy, thus indicating additional targets for potential therapeutic interventions.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnology and National Institute of Neuroscience, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Russo
authors.forename: Daniela
authors.initials: D
authors.lastname: Bonini
authors.forename: Luca La
authors.initials: LL
authors.lastname: Via
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017403:In Situ Hybridization; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D010862:Pilocarpine / Q000633:toxicity*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics; D017393:RNA Editing / Q000187:drug effects; D012326:RNA Splicing / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D021122:Protein Subunits; D012333:RNA, Messenger; D018091:Receptors, AMPA; D010862:Pilocarpine