title: Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine.
abstract: Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.
authors.affiliation: Division of Neurology, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, Rua Pedro de Toledo, 781, 7 andar frente, São Paulo 04039-032, Brazil.
authors.forename: Ibrahim Elias
authors.initials: IE
authors.lastname: Nasseh
authors.forename: Débora
authors.initials: D
authors.lastname: Amado
authors.forename: Esper A
authors.initials: EA
authors.lastname: Cavalheiro
authors.forename: Maria da Graça
authors.initials: Mda G
authors.lastname: Naffah-Mazzacoratti
authors.forename: Célia Harumi
authors.initials: CH
authors.lastname: Tengan
mesh_terms: D000818:Animals; D003292:Convulsants; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D004833:Epilepsy, Temporal Lobe / Q000235:genetics / Q000378:metabolism*; D007696:Kindling, Neurologic; D008297:Male; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*
chemical_list: D003292:Convulsants; D004272:DNA, Mitochondrial; D010862:Pilocarpine; D003576:Electron Transport Complex IV