Mouton Peter R, Chachich Mark E, Quigley Christopher, Spangler Edward, Ingram Donald K
Laboratory of Experimental Gerontology, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224, United States.
Neurosci Lett. 2009 Oct 30;464(3):184-7. doi: 10.1016/j.neulet.2009.08.038. Epub 2009 Aug 20.
Caloric restriction (CR) mitigates neurological damage arising from aging and a variety of other sources, including neuropathology in young adult mice that express single and double transgenic (tg) mutations associated with Alzheimer disease (AD). To evaluate the potential of CR to protect against relatively heavy AD-type pathology, middle-aged (13-14-month-old) mice that co-express two mutations related to familial AD, amyloid precursor protein (APP) and presenilin 1 (PS1), were fed balanced diets with 40% fewer calories than ad libitum-fed controls. Following 18 weeks of treatment, mice were killed and brains were processed for quantification of total volume of amyloid-beta (Abeta) in the hippocampal formation and the overlying neocortex. Computerized stereology confirmed that CR reduced the total Abeta volume by about one-third compared to that in age-matched controls. Thus, CR appears to attenuate the accumulation of AD-type neuropathology in two cortical brain regions of middle-aged dtg APP/PS1 mice. These findings support the view that CR could be a potentially effective, non-pharmacology strategy for reducing relatively heavy Abeta deposition in older adult dtg APP/PS1 mice, and possibly afford similar protection against the onset and progression of AD in older adult humans.
热量限制（CR）可减轻衰老及其他多种原因引起的神经损伤，包括在表达与阿尔茨海默病（AD）相关的单转基因和双转基因（tg）突变的年轻成年小鼠中的神经病理学变化。为了评估热量限制预防相对严重的AD型病理变化的潜力，对共表达两种与家族性AD相关突变（淀粉样前体蛋白（APP）和早老素1（PS1））的中年（13 - 14月龄）小鼠，给予热量比随意进食对照组少40%的均衡饮食。经过18周的治疗后，处死小鼠并对大脑进行处理，以定量海马结构和上方新皮质中β淀粉样蛋白（Aβ）的总体积。计算机辅助立体学证实，与年龄匹配的对照组相比，热量限制使Aβ总体积减少了约三分之一。因此，热量限制似乎减弱了中年双转基因APP/PS1小鼠两个皮质脑区中AD型神经病理学变化的积累。这些发现支持这样一种观点，即热量限制可能是一种潜在有效的非药物策略，可减少老年双转基因APP/PS1小鼠中相对大量的Aβ沉积，并可能为老年人类预防AD的发生和进展提供类似的保护。
