Epilepsy Research 68 (2006) 229–239 Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine Ibrahim Elias Nasseh a , D´ ebora Amado b , Esper A. Cavalheiro b , Maria da Grac ¸a Naffah-Mazzacoratti c , C´ elia Harumi Tengan a,∗ a Division of Neurology, Department of Neurology and Neurosurgery, Universidade Federal de S˜ ao Paulo, Rua Pedro de Toledo, 781, 7 ◦ andar frente, S˜ ao Paulo 04039-032, Brazil b Division of Experimental Neurology, Department of Neurology and Neurosurgery, Universidade Federal de S˜ ao Paulo, Brazil c Department of Biochemistry, Universidade Federal de S˜ ao Paulo, Brazil Received 7 July 2005; received in revised form 13 September 2005; accepted 9 November 2005 Available online 7 December 2005 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 4.8kb 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. © 2005 Elsevier B.V. All rights reserved. Keywords: Epilepsy; Pilocarpine; Mitochondria; Mitochondrial DNA; Cytochrome c oxidase; Free radical ∗ Corresponding author. Tel.: +55 11 5576 4465; fax: +55 11 5081 5005. E-mail address: chtengan@neuro.epm.br (C.H. Tengan). 1. Introduction Several studies suggest that mitochondrial dysfunc- tion may be a contributing factor in the generation of epileptic seizures (Kunz et al., 2000; Kudin et al., 0920-1211/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2005.11.009