Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease
Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease
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DOI：
10.1006/nbdi.2001.0406
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发表时间：
2001-06-01
影响因子：
6.1
通讯作者：
Beal, MF
中科院分区：
文献类型：
--
作者：
Andreassen, OA;Dedeoglu, A;Beal, MF
有大量证据表明亨廷顿舞蹈病（HD）存在生物能量缺陷。肌酸增加脑磷酸肌酸水平，稳定线粒体通透性转变。我们在亨廷顿蛋白n端171个氨基酸片段（N171-82Q）中82个聚谷氨酰胺重复序列产生的HD转基因小鼠模型中检测了肌酸给药的影响，饮食中补充2%肌酸显著提高了存活率，减缓了运动症状的发展，并延缓了体重减轻的开始。肌酸减轻脑萎缩和核内包涵体的形成，减弱纹状体n -乙酰天冬氨酸的减少，通过核磁共振波谱评估，并延缓高血糖的发展。这些结果与在R6/2转基因HD小鼠模型中使用膳食补充肌酸观察到的结果相似，进一步证明了肌酸可能在HD中发挥治疗作用。(C) 2001学术出版社。
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. (C) 2001 Academic Press.