Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease
Open Access
- 7 October 2010
- journal article
- research article
- Published by Wiley in Movement Disorders
- Vol. 26 (1), 130-137
- https://doi.org/10.1002/mds.23258
Abstract
Mitochondrial defects that affect cellular energy metabolism have long been implicated in the etiology of Huntington's disease (HD). Indeed, several studies have found defects in the mitochondrial functions of the central nervous system and peripheral tissues of HD patients. In this study, we investigated the in vivo oxidative metabolism of exercising muscle in HD patients. Ventilatory and cardiometabolic parameters and plasma lactate concentrations were monitored during incremental cardiopulmonary exercise in twenty‐five HD subjects and twenty‐five healthy subjects. The total exercise capacity was normal in HD subjects but notably the HD patients and presymptomatic mutation carriers had a lower anaerobic threshold than the control subjects. The low anaerobic threshold of HD patients was associated with an increase in the concentration of plasma lactate. We also analyzed in vitro muscular cell cultures and found that HD cells produce more lactate than the cells of healthy subjects. Finally, we analyzed skeletal muscle samples by electron microscopy and we observed striking mitochondrial structural abnormalities in two out of seven HD subjects. Our findings confirm mitochondrial abnormalities in HD patients' skeletal muscle and suggest that the mitochondrial dysfunction is reflected functionally in a low anaerobic threshold and an increased lactate synthesis during intense physical exercise. © 2010 Movement Disorder SocietyThis publication has 36 references indexed in Scilit:
- Mutant Huntingtin induces activation of the Bcl-2/adenovirus E1B 19-kDa interacting protein (BNip3)Cell Death & Disease, 2010
- Role of mitochondrial dysfunction in the pathogenesis of Huntington's diseaseBrain Research Bulletin, 2009
- Abnormal morphology of peripheral cell tissues from patients with Huntington diseaseJournal of Neural Transmission, 2009
- Impaired PGC-1α function in muscle in Huntington's diseaseHuman Molecular Genetics, 2009
- Myopathy as a first symptom of Huntington's disease in a Marathon runnerMovement Disorders, 2007
- Cardiac dysfunction in the R6/2 mouse model of Huntington’s diseaseNeurobiology of Disease, 2007
- Lack of improvement of lung diffusing capacity following fluid withdrawal by ultrafiltration in chronic heart failureJournal of the American College of Cardiology, 2000
- Widespread expression of Huntington's disease gene (IT15) protein productNeuron, 1995
- Mitochondrial diseases of muscleCurrent Opinion in Neurology, 1994
- The Benefits of the Low Intensity Training.The Annals of physiological anthropology, 1992