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Article Publish Status: FREE
Abstract Title:

Treadmill exercise rescues mitochondrial function and motor behavior in the CAGknock-in mouse model of Huntington's disease.

Abstract Source:

Chem Biol Interact. 2020 Jan 5 ;315:108907. Epub 2019 Nov 26. PMID: 31778667

Abstract Author(s):

Charles C Caldwell, Giselle M Petzinger, Michael W Jakowec, Enrique Cadenas

Article Affiliation:

Charles C Caldwell

Abstract:

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by polyglutamine (CAG) expansion in the Huntingtin (HTT) gene. The CAGknock-in (KI) mouse model recapitulates the progression of motor symptoms emerging at 12 months of age.

OBJECTIVE: This study was aimed at assessing the effects of exercise, in the form of treadmill running, and examining its impact on motor behavior and markers of metabolism in the CAGKI mouse model of HD after motor symptoms have emerged.

METHODS: CAGKI mice at 13-15 months of age were subjected to treadmill exercise 3 days per week for 1 h per day or remained sedentary. After 12 weeks of exercise brain tissues were analyzed for enzymatic activity including mitochondria Complexes I, II/III, and IV, transglutaminase, aconitase, pyruvate dehydrogenase, and phosphofructokinase1/2. In addition, the concentration was determined for nitrate/nitrite, pyruvate carboxylase, NAD/NADH, and glutamate as well as the ratio of mitochondria and nuclear DNA. Motor behavior was tested using the rotarod.

RESULTS: Exercise resulted in increased [nitrite + nitrate] levels (surmised as nitric oxide), reduced transglutaminase activity, increased aconitase activity with increased tricarboxylic acid-generated reducing equivalents and mitochondrial oxidative phosphorylation complexes activity. Mitochondrial function was strengthened by increases in glycolysis, pyruvate dehydrogenase activity, and anaplerosis component represented by pyruvate carboxylase.

CONCLUSIONS: These changes in mitochondrial function were associated with improved motor performance on the rotarod test. These findings suggest that exercise may have beneficial effects on motor behavior by reversing deficits in mitochondrial function in a rodent model of HD.

Study Type : Animal Study
Additional Links
Therapeutic Actions : Exercise : CK(4855) : AC(736)

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