Mitochondrial dysfunction and ultrastructural damage in the hippocampus of pilocarpine-induced epileptic rat.
Mitochondrial dysfunction has been implicated as a contributing factor in epileptic seizures. Present studies were carried out to decipher seizure-dependent changes in mitochondrial function and ultrastructure in the chronic condition of temporal lobe epilepsy (TLE) induced by pilocarpine in rat hippocampus. Enzyme assay revealed significant depression of the activity of mitochondrial- and nuclear-encoded cytochrome oxidase (COX). Conversely, the activity of nuclear-encoded succinate dehydrogenase (SDH) remained unchanged. Discernible mitochondrial ultrastructural damage, varying from swelling to disruption of membrane, was observed in the hippocampus. Quantitative real-time PCR and Western blotting showed the expression of mitochondrial-encoded COX subunit III (COXIII) dropped significantly during the chronic seizure activity; the corresponding expression of COX subunit IV (COXIV) displayed no significant change. Most likely, our results suggest that dysfunction of mitochondrial COX respiratory enzyme and mitochondrial ultrastructural damage in the hippocampus are associated with prolonged seizure during experimental TLE and mitochondria are more vulnerable to epilepsy.
Gao
Jing
J
Department of Neurology, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China.
Chi
Zhao-Fu
ZF
Liu
Xue-Wu
XW
Shan
Pei-Yan
PY
Wang
Rong
R
D000820:Animal Diseases; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D003576:Electron Transport Complex IV / Q000378:metabolism; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000648:ultrastructure*; D028361:Mitochondrial Diseases / Q000209:etiology*; D010862:Pilocarpine; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013385:Succinate Dehydrogenase / Q000378:metabolism
D012333:RNA, Messenger; D010862:Pilocarpine; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV