mRNA Expression Levels of PGC-1α in a Transgenic and a Toxin Model of Huntington’s Disease

Rita Török, Júlia Anna Kónya, Dénes Zádori, Gábor Veres, Levente Szalárdy, L. Vécsei, P. Klivényi

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalCellular and Molecular Neurobiology
Volume35
Issue number2
DOIs
Publication statusPublished - 2015

Fingerprint

Huntington Disease
Nuclear Respiratory Factors
Cerebellum
Messenger RNA
Up-Regulation
Peroxisome Proliferator-Activated Receptors
Thermogenesis
Organelle Biogenesis
Estrogen Receptors
Transgenic Mice
Respiration
Age Groups
Polymerase Chain Reaction
Brain
Proteins
3-nitropropionic acid
Therapeutics

Keywords

  • 3-Nitropropionic acid
  • FL-PGC-1α
  • Huntington’s disease
  • NT-PGC-1α
  • PGC-1α

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Medicine(all)

Cite this

mRNA Expression Levels of PGC-1α in a Transgenic and a Toxin Model of Huntington’s Disease. / Török, Rita; Kónya, Júlia Anna; Zádori, Dénes; Veres, Gábor; Szalárdy, Levente; Vécsei, L.; Klivényi, P.

In: Cellular and Molecular Neurobiology, Vol. 35, No. 2, 2015, p. 293-301.

Research output: Contribution to journalArticle

Török, Rita ; Kónya, Júlia Anna ; Zádori, Dénes ; Veres, Gábor ; Szalárdy, Levente ; Vécsei, L. ; Klivényi, P. / mRNA Expression Levels of PGC-1α in a Transgenic and a Toxin Model of Huntington’s Disease. In: Cellular and Molecular Neurobiology. 2015 ; Vol. 35, No. 2. pp. 293-301.
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