• Open Access

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

Authors

  • Andrea Ciammola MD,

    Corresponding author
    1. Department of Neurology and Laboratory of Neuroscience, Centro “Dino Ferrari” Università degli Studi di Milano - IRCCS Istituto Auxologico Italiano, Milan, Italy
    • Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, via Spagnoletto 3, 20149 Milan, Italy
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  • Jenny Sassone PhD,

    1. Department of Neurology and Laboratory of Neuroscience, Centro “Dino Ferrari” Università degli Studi di Milano - IRCCS Istituto Auxologico Italiano, Milan, Italy
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  • Monica Sciacco MD,

    1. Department of Neurological Sciences, Centro “Dino Ferrari,” Università di Milano, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy
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  • Niccolò E. Mencacci MD,

    1. Department of Neurology and Laboratory of Neuroscience, Centro “Dino Ferrari” Università degli Studi di Milano - IRCCS Istituto Auxologico Italiano, Milan, Italy
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  • Michela Ripolone PhD,

    1. Department of Neurological Sciences, Centro “Dino Ferrari,” Università di Milano, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy
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  • Caterina Bizzi MD,

    1. Department of Cardiology, S. Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy
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  • Clarissa Colciago PhD,

    1. Department of Neurology and Laboratory of Neuroscience, Centro “Dino Ferrari” Università degli Studi di Milano - IRCCS Istituto Auxologico Italiano, Milan, Italy
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  • Maurizio Moggio MD,

    1. Department of Neurological Sciences, Centro “Dino Ferrari,” Università di Milano, IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena, Milan, Italy
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  • Gianfranco Parati MD,

    1. Department of Cardiology, S. Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy
    2. Department of Clinical Medicine and Prevention, Università di Milano-Bicocca, Milan, Italy
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  • Vincenzo Silani MD,

    1. Department of Neurology and Laboratory of Neuroscience, Centro “Dino Ferrari” Università degli Studi di Milano - IRCCS Istituto Auxologico Italiano, Milan, Italy
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  • Gabriella Malfatto MD

    1. Department of Cardiology, S. Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy
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  • Potential conflict of interest: Nothing to report.

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 Society

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