Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease

O. A. Andreassen; A. Dedeoglu; R. J. Ferrante; B. G. Jenkins; K. L. Ferrante; M. Thomas; A. Friedlich; S. E. Browne; G. Schilling; D. R. Borchelt; S. M. Hersch; C. A. Ross; M. F. Beal

doi:10.1006/nbdi.2001.0406

Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease

O. A. Andreassen, A. Dedeoglu, R. J. Ferrante, B. G. Jenkins, K. L. Ferrante, M. Thomas, A. Friedlich, S. E. Browne, G. Schilling, D. R. Borchelt, S. M. Hersch, C. A. Ross, M. F. Beal

School of Medicine

Research output: Contribution to journal › Article › peer-review

240 Scopus citations

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.

Original language	English (US)
Pages (from-to)	479-491
Number of pages	13
Journal	Neurobiology of Disease
Volume	8
Issue number	3
DOIs	https://doi.org/10.1006/nbdi.2001.0406
State	Published - 2001

Keywords

Creatine
Diabetes
Huntington's
N-acetylaspartate
NMR spectroscopy
Transgenic

ASJC Scopus subject areas

Neurology

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Andreassen, O. A., Dedeoglu, A., Ferrante, R. J., Jenkins, B. G., Ferrante, K. L., Thomas, M., Friedlich, A., Browne, S. E., Schilling, G., Borchelt, D. R., Hersch, S. M., Ross, C. A., & Beal, M. F. (2001). Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiology of Disease, 8(3), 479-491. https://doi.org/10.1006/nbdi.2001.0406

Andreassen, OA, Dedeoglu, A, Ferrante, RJ, Jenkins, BG, Ferrante, KL, Thomas, M, Friedlich, A, Browne, SE, Schilling, G, Borchelt, DR, Hersch, SM, Ross, CA & Beal, MF 2001, 'Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease', Neurobiology of Disease, vol. 8, no. 3, pp. 479-491. https://doi.org/10.1006/nbdi.2001.0406

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title = "Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease",

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.",

keywords = "Creatine, Diabetes, Huntington's, N-acetylaspartate, NMR spectroscopy, Transgenic",

author = "Andreassen, {O. A.} and A. Dedeoglu and Ferrante, {R. J.} and Jenkins, {B. G.} and Ferrante, {K. L.} and M. Thomas and A. Friedlich and Browne, {S. E.} and G. Schilling and Borchelt, {D. R.} and Hersch, {S. M.} and Ross, {C. A.} and Beal, {M. F.}",

note = "Funding Information: This work was supported by The Hereditary Disease Foundation, The Huntington Disease Society of America, The Department of Defense and NIH Grants NS38180 (M.F.B.), NS35255 (R.J.F. and S.M.H.), NS37102, and AG13846 (R.J.F.), and AG12992 (M.F.B. and R.J.F.), AT00613 (R.J.F., S.M.H., and M.F.B.), NS16375 (C.A.R. and D.R.B.), and NS38144 (C.A.R.) the Veterans Administration (R.J.F.), and the Norwegian Research Council (O.A.A.). The secretarial assistance of Sharon Melanson and technical support of Karen Smith and John R. Schleicher are gratefully acknowledged.",

year = "2001",

doi = "10.1006/nbdi.2001.0406",

language = "English (US)",

volume = "8",

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journal = "Neurobiology of Disease",

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AU - Andreassen, O. A.

AU - Dedeoglu, A.

AU - Ferrante, R. J.

AU - Jenkins, B. G.

AU - Ferrante, K. L.

AU - Thomas, M.

AU - Friedlich, A.

AU - Browne, S. E.

AU - Schilling, G.

AU - Borchelt, D. R.

AU - Hersch, S. M.

AU - Ross, C. A.

AU - Beal, M. F.

N1 - Funding Information: This work was supported by The Hereditary Disease Foundation, The Huntington Disease Society of America, The Department of Defense and NIH Grants NS38180 (M.F.B.), NS35255 (R.J.F. and S.M.H.), NS37102, and AG13846 (R.J.F.), and AG12992 (M.F.B. and R.J.F.), AT00613 (R.J.F., S.M.H., and M.F.B.), NS16375 (C.A.R. and D.R.B.), and NS38144 (C.A.R.) the Veterans Administration (R.J.F.), and the Norwegian Research Council (O.A.A.). The secretarial assistance of Sharon Melanson and technical support of Karen Smith and John R. Schleicher are gratefully acknowledged.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease

Abstract

Keywords

ASJC Scopus subject areas

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