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.