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发表于 2007-12-10 08:29 PM
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Alzheimer's Disease (AD)
AD是一种典型得老年痴呆。一般建议通过运动来预防（Marx 2005）。值得指出的是，如果存在缺血损伤，运动会使病情恶化（Eggermont et al 2006）。
动物实验表明，通过限制热量(caloric restriction, CR)就可以预防AD（Qin et al 2006, Halagappa et al 2007）:
Qin et al 2006: 30%CR
Halagappa et al 2007: 40% CR or deprived of food for 24 h every other day.
当然，食物剥夺的时间不能太长，否则也有可能引起AD（Yanagisawa et al 1999）.
看来AD也是一种饮食方式与行为方式失配的产物。值得注意的是，AD的发病率随着年龄的增长而增长，一旦被确诊就没有治疗办法。看来，为了不变成老呆瓜，选择与行为方式匹配的饮食方式是唯一正确的道路。
参考文献
Eggermont L, Swaab D, Luiten P, Scherder E. 2006. Exercise, cognition and Alzheimer's disease: more is not necessarily better. Neurosci Biobehav Rev. 2006;30(4):562-75. Regional hypoperfusion, associated with a reduction in cerebral metabolism, is a hallmark of Alzheimer's disease (AD) and contributes to cognitive decline. Cerebral perfusion and hence cognition can be enhanced by exercise. The present review describes first how the effects of exercise on cerebral perfusion in AD are mediated by nitric oxide (NO) and tissue-type plasminogen activator, the release of which is regulated by NO. A conclusion of clinical relevance is that exercise may not be beneficial for the cognitive functioning of all people with dementia if cardiovascular risk factors are present. The extent to which cardiovascular risk factors play a role in the selection of older people with dementia in clinical studies will be addressed in the second part of the review in which the effects of exercise on cognition are presented. Only eight relevant studies were found in the literature, emphasizing the paucity of studies in this field. Positive effects of exercise on cognition were reported in seven studies, including two that excluded and two that included patients with cardiovascular risk factors. These findings suggest that cardiovascular risk factors do not necessarily undo the beneficial effects of exercise on cognition in cognitively impaired people. Further research is called for, in view of the limitations of the clinical studies reviewed here.
Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, Mattson MP. 2007. Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol Dis. 2007 Apr;26(1):212-20. Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive decline in cognitive function associated with the neuropathological hallmarks amyloid beta-peptide (Abeta) plaques and neurofibrillary tangles. Because aging is the major risk factor for AD, and dietary energy restriction can retard aging processes in the brain, we tested the hypothesis that two different energy restriction regimens, 40% calorie restriction (CR) and intermittent fasting (IF) can protect against cognitive decline in the triple-transgenic mouse model of AD (3xTgAD mice). Groups of 3xTgAD mice were maintained on an ad libitum control diet, or CR or IF diets, beginning at 3 months of age. Half of the mice in each diet group were subjected to behavioral testing (Morris swim task and open field apparatus) at 10 months of age and the other half at 17 months of age. At 10 months 3xTgAD mice on the control diet exhibited reduced exploratory activity compared to non-transgenic mice and to 3xTgAD mice on CR and IF diets. Overall, there were no major differences in performance in the water maze among genotypes or diets in 10-month-old mice. In 17-month-old 3xTgAD mice the CR and IF groups exhibited higher levels of exploratory behavior, and performed better in both the goal latency and probe trials of the swim task, compared to 3xTgAD mice on the control diet. 3xTgAD mice in the CR group showed lower levels of Abeta1-40, Abeta1-42 and phospho-tau in the hippocampus compared to the control diet group, whereas Abeta and phospho-tau levels were not decreased in 3xTgAD mice in the IF group. IF may therefore protect neurons against adverse effects of Abeta and tau pathologies on synaptic function. We conclude that CR and IF dietary regimens can ameliorate age-related deficits in cognitive function by mechanisms that may or may not be related to Abeta and tau pathologies.
Marx J. 2005. Neuroscience. Preventing Alzheimer's: a lifelong commitment? Science. 2005 Aug 5;309(5736):864-6(见附件).
Qin W, Chachich M, Lane M, Roth G, Bryant M, de Cabo R, Ottinger MA, Mattison J, Ingram D, Gandy S, Pasinetti GM. 2006. Calorie restriction attenuates Alzheimer's disease type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). J Alzheimers Dis. 2006 Dec;10(4):417-22. Recent studies from our laboratories and others suggest that calorie restriction (CR) may benefit Alzheimer's disease (AD) by preventing amyloid-beta (Abeta) neuropathology in the mouse models of AD. Moreover, we found that promotion of the NAD+-dependent SIRT1 mediated deacetylase activity, a key regulator in CR extension of life span, may be a mechanism by which CR influences AD-type neuropathology. In this study we continued to explore the role of CR in AD-type brain amyloidosis in Squirrel monkeys (Saimiri sciureus). Monkeys were maintained on the normal and CR diets throughout the entire lifespan until they died of natural causes. We found that 30% CR resulted in reduced contents of Abeta1-40 and Abeta1-42 peptides in the temporal cortex of Squirrel monkeys, relative to control (CON) fed monkeys. The decreased contents of cortical Abeta peptide inversely correlated with SIRT1 protein concentrations in the same brain region; no detectable change in total full-length amyloid-beta protein precursor (AbetaPP) level was found. Most interestingly, we found that 30% CR resulted in a select elevation of alpha- but not beta- or gamma- secretase activity which coincided with decreased ROCK1 protein content in the same brain region, relative to CON group. Collectively, the study suggests that investigation of the role of CR in non-human primates may provide a valuable approach for further clarifying the role of CR in AD.
Yanagisawa M, Planel E, Ishiguro K, Fujita SC. 1999. Starvation induces tau hyperphosphorylation in mouse brain: implications for Alzheimer's disease. FEBS Lett. 1999 Nov 19;461(3):329-33. Hyperphosphorylated tau is the major component of paired helical filaments in neurofibrillary tangles found in Alzheimer's disease brains, and tau hyperphosphorylation is thought to be a critical event in the pathogenesis of this disease. The objective of this study was to reproduce tau hyperphosphorylation in an animal model by inducing hypoglycemia. Food deprivation of mice for 1 to 3 days progressively enhanced tau hyperphosphorylation in the hippocampus, to a lesser extent in the cerebral cortex, but the effect was least in the cerebellum, in correspondence with the regional selectivity of tauopathy in Alzheimer's disease. This hyperphosphorylation was reversible by refeeding for 1 day. We discuss possible mechanisms of this phenomenon, and propose the starved mouse as a simple model to study in vivo tau phosphorylation and dephosphorylation which are altered in Alzheimer's disease.
[ 本帖最后由 刘承宜 于 2007-12-10 09:24 PM 编辑 ] |
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