ENVIRONMENTAL ENRICHMENT EFFECTS IN ALZHEIMER'S DISEASE TRANSGENIC MICE

虽然回顾性研究表明，高精神活动的终身模式是预防阿尔茨海默病（AD），前瞻性纵向研究尚未完成。此外，在对照临床研究中尚未充分评估社交和/或体力活动对AD风险降低的贡献，也没有评估AD患者长期强化认知康复的潜在益处。AD转基因小鼠的可用性使得在完全对照的纵向研究中调查这些问题成为可能。我们的初步研究表明，“完全”的环境富集（例如，认知、社会和体力活动）对AD转基因小鼠的认知障碍既有保护作用又有治疗作用？而不影响大脑β-淀粉样蛋白的沉积。本项目将首先阐明每一个组织的作用， 贡献组件（例如，认知，社会和身体）的保护能力，完成 环境富集;这种富集的贡献成分的分离在临床研究中是不可能实现的。其次，本项目将评估连续和会话限制的环境丰富作为认知受损的AD转基因小鼠的治疗的潜力。所有AD患者的认知康复治疗都是有疗程限制的，因此在AD转基因模型中研究该方案具有重要意义。第三，将评估各种脑神经病理和神经化学过程，这些过程可能与环境富集或其各种成分活动提供的认知益处有关。这些过程包括神经发生、神经变性、氧化应激、神经炎症和生长因子调节。总的来说，这个项目的研究 具有重要的公共卫生意义，因为它们研究了“可改变”因素（认知、社会、身体活动）预防或治疗AD的潜力，并提供了对可能参与其中的细胞/分子机制的重要见解。

Although retrospective studies suggest that a lifelong pattern of high mental activity is protective against Alzheimer's Disease (AD), prospective longitudinal studies have not been done. As well, the contribution of social and/or physical activity to AD risk-reduction has not been adequately evaluated in controlled clinical studies nor has the potential benefit of long-term, intensive cognitive rehabilitation in AD patients. The availability of AD transgenic mice make it possible to investigate these issues in fully-controlled longitudinal studies. Our preliminary studies indicate that "complete" environmental enrichment (e.g., cognitive, social, and physical activity) is both protective and therapeutic against cognitive impairment in AD transgenic mice ? this, without affecting brain beta-amyloid deposition. The present project will first elucidate the role of each contributing component (e.g., cognitive,social, and physical) to the protective ability of complete environmental enrichment; this isolation of enrichment's contributing components is impossible to achieve in clinical studies. Second, this project will evaluate the potential of both continous and session-restricted environmental enrichment as a treatment to cognitively-impaired AD transgenic mice. All cognitive rehabilitative therapeutic in AD patients are session-restricted, so it is important to investigate this protocol in AD transgenic models. Third, a variety of brain neuropathologic and neurochemical processes will be assessed that could be mechanistically involved in the cognitive benefits provided by environmental enrichment or it's various component activities. These processes include neurogenesis, neurodegeneration, oxidative stress, neuroinflammation, and growth factor modulation. Collectively, the studies of this project are of substantial public health significance because they investigate the potential for "modifiable" factors (cognitive, social, physical activity) to protective against or treat AD, as well as provide important insight into likely cellular/molecular mechanisms that may be involved therein.