Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease.
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.
Andreassen
O A
OA
Neurochemistry Laboratory, Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusets, USA.
Dedeoglu
A
A
Ferrante
R J
RJ
Jenkins
B G
BG
Ferrante
K L
KL
Thomas
M
M
Friedlich
A
A
Browne
S E
SE
Schilling
G
G
Borchelt
D R
DR
Hersch
S M
SM
Ross
C A
CA
Beal
M F
MF
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001786:Blood Glucose; D001923:Brain Chemistry / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003404:Creatinine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects*; D017072:Neostriatum / Q000187:drug effects / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D009929:Organ Size; D015996:Survival Rate
D001786:Blood Glucose; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D007328:Insulin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D001224:Aspartic Acid; C000179:N-acetylaspartate; D003404:Creatinine