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

Publication ,  Journal Article
Ferrante, RJ; Andreassen, OA; Jenkins, BG; Dedeoglu, A; Kuemmerle, S; Kubilus, JK; Kaddurah-Daouk, R; Hersch, SM; Beal, MF
Published in: J Neurosci
June 15, 2000

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.

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Published In

J Neurosci

DOI

ISSN

0270-6474

Publication Date

June 15, 2000

Volume

20

Issue

12

Start / End Page

4389 / 4397

Location

United States

Related Subject Headings

  • Nuclear Proteins
  • Neuroprotective Agents
  • Neurons
  • Neurology & Neurosurgery
  • Nerve Tissue Proteins
  • Motor Activity
  • Mice, Inbred Strains
  • Mice
  • Male
  • Magnetic Resonance Imaging
 

Citation

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Ferrante, R. J., Andreassen, O. A., Jenkins, B. G., Dedeoglu, A., Kuemmerle, S., Kubilus, J. K., … Beal, M. F. (2000). Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci, 20(12), 4389–4397. https://doi.org/10.1523/JNEUROSCI.20-12-04389.2000
Ferrante, R. J., O. A. Andreassen, B. G. Jenkins, A. Dedeoglu, S. Kuemmerle, J. K. Kubilus, R. Kaddurah-Daouk, S. M. Hersch, and M. F. Beal. “Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease.J Neurosci 20, no. 12 (June 15, 2000): 4389–97. https://doi.org/10.1523/JNEUROSCI.20-12-04389.2000.
Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000 Jun 15;20(12):4389–97.
Ferrante, R. J., et al. “Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease.J Neurosci, vol. 20, no. 12, June 2000, pp. 4389–97. Pubmed, doi:10.1523/JNEUROSCI.20-12-04389.2000.
Ferrante RJ, Andreassen OA, Jenkins BG, Dedeoglu A, Kuemmerle S, Kubilus JK, Kaddurah-Daouk R, Hersch SM, Beal MF. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000 Jun 15;20(12):4389–4397.

Published In

J Neurosci

DOI

ISSN

0270-6474

Publication Date

June 15, 2000

Volume

20

Issue

12

Start / End Page

4389 / 4397

Location

United States

Related Subject Headings

  • Nuclear Proteins
  • Neuroprotective Agents
  • Neurons
  • Neurology & Neurosurgery
  • Nerve Tissue Proteins
  • Motor Activity
  • Mice, Inbred Strains
  • Mice
  • Male
  • Magnetic Resonance Imaging