title: mRNA expression levels of PGC-1α in a transgenic and a toxin model of Huntington's disease.
abstract: Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1 alpha (PGC-1α) is involved in the regulation of mitochondrial biogenesis, respiration, and adaptive thermogenesis. The full-length PGC-1α (FL-PGC-1α) comprises multiple functional domains interacting with several transcriptional regulatory factors such as nuclear respiratory factors, estrogen-related receptors, and PPARs; however, a number of PGC-1α splice variants have also been reported recently. In this study, we examined the expression levels of FL-PGC-1α and N-truncated PGC-1α (NT-PGC-1α), a shorter but functionally active splice variant of PGC-1α protein, in N171-82Q transgenic and 3-nitropropionic acid-induced murine model of Huntington's disease (HD). The expression levels were determined by RT-PCR in three brain areas (striatum, cortex, and cerebellum) in three age groups (8, 12, and 16 weeks). Besides recapitulating prior findings that NT-PGC-1α is preferentially increased in 16 weeks of age in transgenic HD animals, we detected age-dependent alterations in both models, including a cerebellum-predominant upregulation of both PGC-1α variants in transgenic mice, and a striatum-predominant upregulation of both PGC-1α variants after acute 3-nitropropionic acid intoxication. The possible relevance of this expression pattern is discussed. Based on our results, we assume that increased expression of PGC-1α may serve as a compensatory mechanism in response to mitochondrial damage in transgenic and toxin models of HD, which may be of therapeutic relevance.
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Szeged, Semmelweis u. 6, Szeged, 6725, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Török
authors.forename: Júlia Anna
authors.initials: JA
authors.lastname: Kónya
authors.forename: Dénes
authors.initials: D
authors.lastname: Zádori
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.forename: Levente
authors.initials: L
authors.lastname: Szalárdy
authors.forename: László
authors.initials: L
authors.lastname: Vécsei
authors.forename: Péter
authors.initials: P
authors.lastname: Klivényi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009574:Nitro Compounds; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011422:Propionates; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D009574:Nitro Compounds; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D011422:Propionates; D012333:RNA, Messenger; D014157:Transcription Factors; C015392:3-nitropropionic acid