RT Journal Article
SR Electronic
T1 Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4389
OP 4397
DO 10.1523/JNEUROSCI.20-12-04389.2000
VO 20
IS 12
A1 Robert J. Ferrante
A1 Ole A. Andreassen
A1 Bruce G. Jenkins
A1 Alpaslan Dedeoglu
A1 Stefan Kuemmerle
A1 James K. Kubilus
A1 Rima Kaddurah-Daouk
A1 Steven M. Hersch
A1 M. Flint Beal
YR 2000
UL http://www.jneurosci.org/content/20/12/4389.abstract
AB Huntington's disease (HD) is a progressive neurodegenerative illness for which there is no effective therapy. We examined whether creatine, which may exert neuroprotective effects by increasing phosphocreatine levels or by stabilizing the mitochondrial permeability transition, has beneficial effects in a transgenic mouse model of HD (line 6/2). Dietary creatine supplementation significantly improved survival, slowed the development of brain atrophy, and delayed atrophy of striatal neurons and the formation of huntingtin-positive aggregates in R6/2 mice. Body weight and motor performance on the rotarod test were significantly improved in creatine-supplemented R6/2 mice, whereas the onset of diabetes was markedly delayed. Nuclear magnetic resonance spectroscopy showed that creatine supplementation significantly increased brain creatine concentrations and delayed decreases in N-acetylaspartate concentrations. These results support a role of metabolic dysfunction in a transgenic mouse model of HD and suggest a novel therapeutic strategy to slow the pathological process.