title: Impact of exercise on mitochondrial transcription factor expression and damage in the striatum of a chronic mouse model of Parkinson's disease.
abstract: The etiology of neurodegenerative disorders like Parkinson's disease remains unknown, although many genetic and environmental factors are suggested as likely causes. Neuronal oxidative stress and mitochondrial dysfunction have been implicated as possible triggers for the onset and progression of Parkinson's neurodegeneration. We have recently shown that long-term treadmill exercise prevented neurological, mitochondrial and locomotor deficits in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid-induced mouse model of Parkinson's disease that was originally established in our laboratory. In the present study, we further demonstrated that long-term exercise attenuated both cytochrome c release and elevated levels of p53, which are known to be associated with mitochondrial dysfunction in the striatum of this chronic model. On the other hand, the expressions of mitochondrial transcription factor A and peroxisome proliferator-activated receptor gamma coactivator 1α were unexpectedly upregulated in the striatum of this chronic model, but long-term exercise training brought their levels down closer to normal. Our findings suggest that maintaining normal mitochondrial function is essential for preventing the process of Parkinson's disease-like neurodegeneration, whereas stimulating the mitochondrial transcription factors for biogenesis is not obligatory.
authors: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.
authors: Gaurav
authors: G
authors: Patki
authors: Yuen-Sum
authors: YS
authors: Lau
mesh_terms: D000277:Adjuvants, Pharmaceutic / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D002908:Chronic Disease; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D045304:Cytochromes c / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005080:Exercise Test; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism; D020267:MPTP Poisoning / Q000139:chemically induced / Q000473:pathology* / Q000534:rehabilitation*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000379:methods*; D011339:Probenecid / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000277:Adjuvants, Pharmaceutic; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; C081930:Tfam protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D045304:Cytochromes c; D011339:Probenecid