Herbst 2015 Neuroscience
|Herbst EA, Holloway GP (2015) Exercise training normalizes mitochondrial respiratory capacity within the striatum of the R6/1 model of Huntington's disease. Neuroscience 303:515-23.|
Abstract: Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive cell loss in the striatum and cerebral cortex, leading to a decline in motor control and eventually death. The mechanisms promoting motor dysfunction are not known, however loss of mitochondrial function and content has been observed, suggesting that mitochondrial dysfunction may contribute to HD phenotype. Recent work has demonstrated that voluntary wheel running reduces hindlimb clasping in the R6/1 mouse model of HD, which we hypothesized may be due to preservation of mitochondrial content with exercise. Therefore, we investigated the role of chronic exercise training on preventing symptom progression and the loss of mitochondrial content in HD. Exercising R6/1 mice began training at 7 wks of age and continued for 10 or 20 wks. At 17 wks of age, R6/1 mice displayed a clasping phenotype without showing changes in mitochondrial respiration or protein content in either the cortex or striatum, suggesting mitochondrial dysfunction is not necessary for the progression of symptoms. At 27 wks of age, R6/1 mice demonstrated no additional changes in mitochondrial content or respiration within the cortex, but displayed loss of protein in complexes I and III of the striatum, which was not present in exercise-trained R6/1 mice. Mitochondrial respiration was also elevated in the striatum of R6/1 mice at 27 wks, which was prevented with exercise training. Together, the present study provides evidence that mitochondrial dysfunction is not necessary for the progression of hindlimb clasping in R6/1 mice, and that exercise partially prevents changes in mitochondrial content and function that occur late in HD.
• Keywords: Huntington’s disease, Clasping phenotype, Exercise, Mitochondrial dysfunction, Neurodegeneration
• O2k-Network Lab: CA Guelph Holloway GP
Labels: MiParea: Respiration, mtDNA;mt-genetics, Exercise physiology;nutrition;life style Pathology: Neurodegenerative
Organism: Mouse Tissue;cell: Nervous system Preparation: Permeabilized tissue Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III
Coupling state: OXPHOS Pathway: N, S, NS HRR: Oxygraph-2k