Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Ferrante, RJ; Andreassen, OA; Jenkins, BG; Dedeoglu, A; Kuemmerle, S; Kubilus, JK; Kaddurah-Daouk, R; Hersch, SM; Beal, MF

Published Date

  • June 15, 2000

Published In

Volume / Issue

  • 20 / 12

Start / End Page

  • 4389 - 4397

PubMed ID

  • 10844007

Pubmed Central ID

  • PMC6772461

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.20-12-04389.2000


  • eng

Conference Location

  • United States