title: Variations of ATP and its metabolites in the hippocampus of rats subjected to pilocarpine-induced temporal lobe epilepsy.
abstract: Although purinergic receptor activity has lately been associated with epilepsy, little is known about the exact role of purines in epileptogenesis. We have used a rat model of temporal lobe epilepsy induced by pilocarpine to study the dynamics of purine metabolism in the hippocampus during different times of status epilepticus (SE) and the chronic phase. Concentrations of adenosine 5'-triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine in normal and epileptic rat hippocampus were determined by microdialysis in combination with high-performance liquid chromatography (HPLC). Extracellular ATP concentrations did not vary along 4 h of SE onset. However, AMP concentration was elevated during the second hour, whereas ADP and adenosine concentrations augmented during the third and fourth hour following SE. During chronic phase, extracellular ATP, ADP, AMP, and adenosine concentrations decreased, although these levels again increased significantly during spontaneous seizures. These results suggest that the increased turnover of ATP during the acute period is a compensatory mechanism able to reduce the excitatory role of ATP. Increased adenosine levels following 4 h of SE may contribute to block seizures. On the other hand, the reduction of purine levels in the hippocampus of chronic epileptic rats may result from metabolic changes and be part of the mechanisms involved in the onset of spontaneous seizures. This work provides further insights into purinergic signaling during establishment and chronic phase of epilepsy.
authors.affiliation: Departamento de Neurologia e Neurocirurgia, Disciplina de Neurociências, Universidade Federal de São Paulo, UNIFESP, Rua Pedro de Toledo, 669 - 2° andar, CEP 04039-032, São Paulo, Brazil.|Laboratório de Reabilitação do Equilíbrio Corporal e Inclusão Social, Universidade Anhanguera de São Paulo (UNIAN), São Paulo, Brazil.
authors.forename: Flávia
authors.identifier: 0000-0002-9138-4438
authors.initials: F
authors.lastname: Doná
authors.affiliation: Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Isaltino Marcelo
authors.initials: IM
authors.lastname: Conceição
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Henning
authors.initials: H
authors.lastname: Ulrich
authors.affiliation: Departamento Fisiologia, Disciplina de Neurofisiologia e Fisiologia Endócrina, UNIFESP, São Paulo, Brazil.
authors.forename: Eliane Beraldi
authors.initials: EB
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Thalma Ariani
authors.initials: TA
authors.lastname: Freitas
authors.affiliation: Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Ana Leonor Abrahao
authors.initials: AL
authors.lastname: Nencioni
authors.affiliation: Departamento de Neurologia e Neurocirurgia, Disciplina de Neurociências, Universidade Federal de São Paulo, UNIFESP, Rua Pedro de Toledo, 669 - 2° andar, CEP 04039-032, São Paulo, Brazil. fernandesepm@gmail.com.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: da Silva Fernandes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003292:Convulsants; D010862:Pilocarpine; D000255:Adenosine Triphosphate
keywords: ATP metabolism; Adenosine; HPLC; Microdialysis; Temporal lobe epilepsy