A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington's disease.
A ketogenic diet delays weight loss and does not impair working memory or motor function in the R6/2 1J mouse model of Huntington's disease.
复制标题
DOI：
10.1016/j.physbeh.2011.04.001
复制
发表时间：
2011-07-06
影响因子：
2.9
通讯作者：
Masino, Susan A.
中科院分区：
文献类型：
--
作者：
Ruskin, David N.;Ross, Jessica L.;Kawamura, Masahito, Jr.;Ruiz, Tiffany L.;Geiger, Jonathan D.;Masino, Susan A.
关键词：
生酮饮食含有高脂肪和低碳水化合物，长期以来一直被用作药物顽固性癫痫和小儿癫痫的抗惊厥治疗。此外，生酮饮食已被证明对急性和慢性脑损伤具有神经保护作用，包括对各种啮齿动物神经变性模型的有益作用。亨廷顿氏病是一种进行性神经退行性疾病，以神经、行为和代谢功能障碍为特征，生酮饮食已被证明可以增加能量分子和线粒体功能。我们在亨廷顿氏病转基因小鼠模型（r6 / 21j）中测试了生酮饮食的影响，重点关注终身行为和生理影响。匹配的雄性和雌性野生型和转基因小鼠在6周龄时保持对照饮食或切换到自由喂养的生酮饮食。我们发现生酮饮食对任何行为参数测试（运动活动和协调，工作记忆）没有负面影响，寿命也没有显著变化。进行性体重减轻是亨廷顿氏病的一个显著特征，然而我们发现生酮饮食——通常会导致正常动物体重减轻——延缓了转基因小鼠体重的减轻。这些结果表明，代谢疗法可以为亨廷顿氏病提供重要的益处，而不会产生负面的行为或生理后果。
Ketogenic diets are high in fat and low in carbohydrates, and have long been used as an anticonvulsant therapy for drug-intractable and pediatric epilepsy. Additionally, ketogenic diets have been shown to provide neuroprotective effects against acute and chronic brain injury, including beneficial effects in various rodent models of neurodegeneration. Huntington’s disease is a progressive neurodegenerative disease characterized by neurological, behavioral and metabolic dysfunction, and ketogenic diets have been shown to increase energy molecules and mitochondrial function. We tested the effects of a ketogenic diet in a transgenic mouse model of Huntington’s disease (R6/2 1J), with a focus on life-long behavioral and physiological effects. Matched male and female wild-type and transgenic mice were maintained on a control diet or were switched to a ketogenic diet fed ad libitum starting at six weeks of age. We found no negative effects of the ketogenic diet on any behavioral parameter tested (locomotor activity and coordination, working memory) and no significant change in lifespan. Progressive weight loss is a hallmark feature of Huntington’s disease, yet we found that the ketogenic diet - which generally causes weight loss in normal animals - delayed the reduction in body weight of the transgenic mice. These results suggest that metabolic therapies could offer important benefits for Huntington’s disease without negative behavioral or physiological consequences.
登录
查看更多内容
DOI：
10.1073/pnas.97.10.5440
发表时间：
2000-05-09
影响因子：
11.1
作者：
Kashiwaya, Y;Takeshima, T;Veech, RL
通讯作者：
Veech, RL
影响因子：
3.8
作者：
Kang, Hoon-Chul;Kim, Heung Dong;Han, Si Hoon
通讯作者：
Han, Si Hoon
影响因子：
15.9
作者：
Izumi, Y;Ishii, K;Zorumski, CF
通讯作者：
Zorumski, CF
影响因子：
14.5
作者：
Lawrence, AD;Sahakian, BJ;Robbins, TW
通讯作者：
Robbins, TW
影响因子：
30.8
作者：
DUYAO, M;AMBROSE, C;MACDONALD, M
通讯作者：
MACDONALD, M