Changes Of Expression Of Mitochondrial Cytochrome Oxidase Subunits Ⅰ And Ⅳ In The Hippocampus Of Pilocarpine-treated Rat

Objective Mitochondrial respiratory chain is comprised of four multisubunit enzyme complexes. All subunits of SDH (complex II of respiratory chain) are nuclear encoded , while subunit I-III of COX (complex IV of respiratory chain) are mitochondrial encoded and subunit IV-XIII of COX are nuclear encoded. . To investigate the effects of epilepsy on expression of cytochrome oxidase(COX) subnuits I (COX I) and IV (COX IV) encoded by mtDNA and nDNA respectively in hippocampusof the epileptic model induced by pilocarpine in rat.Methods 60 healthy Male Wistar rats were divided randomly into saline control group,acute period groups (3h), silent period group (7d) , chronic period group(45d) after status epilepticus(SE) and group which received pilocarpine (PILO) but did not develop SE.Rats were killed respectly at 3hour,7day and 45d after SE. The expression of COX I and COX IV in rat hippocampus were detected respectively by immunohistochemical staining and real time quantitative PCR(RQ-PCR).Results An significant increase in COX I staining was observed in neuronal cell bodies distributed throughout the hippocampus(CAl, CA2, CA3, dentate gyrus) of rats killed 3h after SE, when compared to the saline-treated group On day 7 after SE, the immunoreactivity was slowly reducedand the immunoreactivity of cell bodies was restricted predominantly to the dentate gyrus, and CA3 regions of the hippocampus. The chronic period (45d) showed decreased staining with the findings indicating neuronal degeneration such as condensation of cell bodies, vacuolization and rearrangement of pyramidal cell layers in the CA3 of the hippocampus. COX I mRNA showed significantly increased expression in the group at 3h after SE(P<0.001)when compared with the control group. The silent group presented similar levels of expression of COX I, but the chronic group showed significantly decreased level in respect to the control group(P<0.001). Slightly increased, but not significant expression of COXTV was found in acute(3h) group , then decreased slightly and remained constant during the following days of epilepsy compared with saline-treated animals. animals that did not respond to PILO in our study showed similar results with that of control group.Conclusions The epileptic model induced by pilocarpine in rats is successful in study the relation between epilepsy and mitochondria;Dysfunction of COX in the hippocampus are associated with prolonged seizure during experimental temporal lobe epilepsy and mitochondria are more vulnerable to epilepsy.