Metabolic changes over the course of aging in a mouse model of tau deposition.
Metabolic changes over the course of aging in a mouse model of tau deposition.
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DOI：
10.1016/j.neurobiolaging.2016.04.013
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发表时间：
2016-08
影响因子：
4.2
通讯作者：
Morgan D
中科院分区：
文献类型：
--
作者：
Joly-Amado A;Serraneau KS;Brownlow M;Marín de Evsikova C;Speakman JR;Gordon MN;Morgan D
在阿尔茨海默病患者中，体重减轻和食物摄取障碍通常出现在认知能力下降和诊断之前，已被广泛报道。此前，我们观察到过度表达tau的转基因小鼠似乎比非转基因小鼠吃了更多的食物，但体重却更轻。因此，本纵向研究测量了tau沉积Tg4510小鼠模型在整个生命周期内代谢状态变化的时间进程。尽管Tg4510小鼠的体重在2个月大时与非转基因小鼠相当，但Tg4510小鼠在年龄较大时体重较轻。伴随而来的是tau病理的积累和24小时周期中所有阶段的活动显著增加。静息代谢率在7个月龄时也有所增加。在接近Tg4510寿命结束的12个月时，有一个衰减期，静息代谢率显著下降，尽管保持了多动。在已知阿尔茨海默病能量代谢变化的背景下，讨论了tau沉积的小鼠模型中代谢的这些不同变化。
Weight loss and food intake disturbances that often precede cognitive decline and diagnosis have been extensively reported in Alzheimer’s disease patients. Previously, we observed that transgenic mice overexpressing tau seemed to eat more food, yet weigh less than non-transgenic littermates. Thus the present longitudinal study measured the time course of changes in metabolic state over the lifespan of the tau depositing Tg4510 mouse model of tau deposition. Although body weight was comparable to non-transgenic littermates at 2 months of age, Tg4510 mice weighed less at older ages. This was accompanied by the accumulation of tau pathology and by dramatically increased activity in all phases of the 24-hour cycle. Resting metabolic rate was also increased at 7 months of age. At 12 months near the end of the Tg4510 lifespan, there was a wasting phase, with a considerable decrease of resting metabolic rate, although hyperactivity was maintained. These diverse changes in metabolism in a mouse model of tau deposition are discussed in the context of known changes in energy metabolism in Alzheimer’s disease.