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

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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.

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Acknowledgments

This research was supported by TÁMOP-4.2.2.A-11/1/KONV-2012-0052, MTA-SZTE Neuroscience Research Group and Hungarian Brain Research Program—Grant No. KTIA_NAP_13-A_III/9. Furthermore, this research was realized in the frames of TÁMOP 4.2.4.A/2-11-1-2012-0001 and TÁMOP 4.2.4. A/1-11-1-2012-0001 National Excellence Programs—Elaborating and operating an inland student and researcher personal support system. The projects were subsidized by the European Union and co-financed by the European Social Fund.

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The authors declare there is no conflict of interest.

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Authors and Affiliations

  1. Department of Neurology, Faculty of Medicine, University of Szeged, Semmelweis u. 6, Szeged, 6725, Hungary

    Rita Török, Júlia Anna Kónya, Dénes Zádori, Gábor Veres, Levente Szalárdy, László Vécsei & Péter Klivényi

  2. MTA-SZTE Neuroscience Research Group, Semmelweis u. 6, Szeged, 6725, Hungary

    László Vécsei

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  1. Rita Török
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Correspondence to Péter Klivényi.

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Török, R., Kónya, J.A., Zádori, D. et al. mRNA Expression Levels of PGC-1α in a Transgenic and a Toxin Model of Huntington’s Disease. Cell Mol Neurobiol 35, 293–301 (2015). https://doi.org/10.1007/s10571-014-0124-z

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