Low anaerobic threshold and increased skeletal muscle lactate production in subjects with Huntington's disease

• Published in: Movement disorders Vol. 26; no. 1; pp. 130 - 137
• Main Authors: Ciammola, Andrea, Sassone, Jenny, Sciacco, Monica, Mencacci, Niccolò E., Ripolone, Michela, Bizzi, Caterina, Colciago, Clarissa, Moggio, Maurizio, Parati, Gianfranco, Silani, Vincenzo, Malfatto, Gabriella
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.01.2011; Wiley
• Subjects: Adult; Aged; anaerobic threshold; Anaerobic Threshold - physiology; Analysis of Variance; Biological and medical sciences; Cells, Cultured; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Heart - physiology; Humans; Huntington Disease - pathology; Huntington Disease - physiopathology; Huntington's disease; Lactic Acid - blood; Lactic Acid - metabolism; Male; Medical sciences; Microscopy, Electron, Transmission - methods; Middle Aged; mitochondria; Mitochondria, Muscle - pathology; Mitochondria, Muscle - ultrastructure; Muscle, Skeletal - cytology; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscle, Skeletal - ultrastructure; Neurology; Respiration; skeletal muscle; Young Adult; Human; Nervous system diseases; Huntington disease; Striated muscle; Huntington's disease; Genetic disease; Cerebral disorder; Lactates; Mitochondria; Central nervous system disease; Anaerobic threshold; Degenerative disease; Lactic acid; skeletal muscle; Extrapyramidal syndrome
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.23258

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 Society