title: Impaired mitochondrial biogenesis in hippocampi of rats with chronic seizures.
abstract: Mitochondrial dysfunction has been suggested to be a contributing factor of epilepsy, but the underlying mechanisms are not completely explored. Mitochondrial biogenesis is involved in regulation of mitochondrial content, morphology, and function. In the current study, we show mitochondrial biogenesis severely impaired in hippocampi of rats with chronic seizures induced by pilocarpine, as evidenced by decreased mitochondrial DNA (mtDNA) content and decreased mtDNA-encoded protein level. Furthermore, we show mtDNA transcription and replication reduced in rats with chronic seizures. These defects were independent of downregulation of mitochondrial biogenesis-related factors, such as peroxisome proliferator-activated receptor gamma coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A (Tfam), but depended on reduced Tfam-DNA binding activity. The present study suggests novel mechanisms for mitochondrial dysfunction during chronic seizures.
authors.affiliation: Department of Neurology, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: Y
authors.initials: Y
authors.lastname: Lin
authors.forename: N
authors.initials: N
authors.lastname: Xie
authors.forename: Y
authors.initials: Y
authors.lastname: Xue
authors.forename: H
authors.initials: H
authors.lastname: Tao
authors.forename: C
authors.initials: C
authors.lastname: Rui
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: L
authors.initials: L
authors.lastname: Cao
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Chi
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004272:DNA, Mitochondrial / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D010862:Pilocarpine