Neurobiology of Disease (Jun 2001)
Creatine Increases Survival and Delays Motor Symptoms in a Transgenic Animal Model of Huntington's Disease
- Ole A. Andreassen,
- Alpaslan Dedeoglu,
- Robert J. Ferrante,
- Bruce G. Jenkins,
- Kimberly L. Ferrante,
- Melissa Thomas,
- Avi Friedlich,
- Susan E. Browne,
- Gabriele Schilling,
- David R. Borchelt,
- Steven M. Hersch,
- Christopher A. Ross,
- M.Flint Beal
Affiliations
- Ole A. Andreassen
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Alpaslan Dedeoglu
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Robert J. Ferrante
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Bruce G. Jenkins
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Kimberly L. Ferrante
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Melissa Thomas
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Avi Friedlich
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Susan E. Browne
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Gabriele Schilling
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- David R. Borchelt
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Steven M. Hersch
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Christopher A. Ross
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- M.Flint Beal
- Neurochemistry Laboratory, Neurology Service, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, MGH-NMR Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Neurology Service, Department of Radiology, Molecular Endocrinology Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Geriatric Research Education and Clinical Center, Bedford VA Medical Center, Bedford, Massachusetts; Department of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts; Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, New York; Department of Pathology, Johns Hopkins University, Baltimore, Maryland; Department of Neurology, Emory University, Atlanta, Georgia; Departments of Psychiatry and Neuroscience, Johns Hopkins University, Baltimore, Maryland
- Journal volume & issue
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Vol. 8,
no. 3
pp. 479 – 491
Abstract
There is substantial evidence for bioenergetic defects in Huntington's disease (HD). Creatine administration increases brain phosphocreatine levels and it stabilizes the mitochondrial permeability transition. We examined the effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin (N171-82Q). Dietary supplementation of 2% creatine significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss. Creatine lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate as assessed by NMR spectroscopy, and delayed the development of hyperglycemia. These results are similar to those observed using dietary creatine supplementation in the R6/2 transgenic mouse model of HD and provide further evidence that creatine may exert therapeutic effects in HD.
