Bidirectional Structural and Functional Plasticity in the Aging Brain.

衰老大脑的双向结构和功能可塑性。

• 批准号: RGPIN-2018-04829
• 负责人: Christie, Brian
• 金额: $ 2.91万
• 依托单位: University of Victoria
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=647667
• 关键词: Bidirectional; Structural; Functional; Plasticity; Aging

The process of aging can negatively impact an individual's cognitive capacity, however there is significant variability across individuals and the reasons for this are the subject of debate. We propose to look at how exercise can impact two theoretical concepts, cognitive capacity and cognitive reserve, in the aged brain. Cognitive capacity is a term that refers to the mechanisms that underlie how we learn, remember and problem solve, and can be assessed using either behavioral tests or electrophysiological analyses. Cognitive reserve is used to describe factors that optimize or promote neurological resiliency in the aged brain, helping to promote higher levels of cognitive functioning. It has been proposed that increases in brain structure may enhance cognitive reserve.***There is considerable evidence that exercise can improve both cognitive capacity and cognitive reserve, however the mechanisms responsible for the benefits of exercise remain to be fully elucidated. In these experiments we will determine if early exposure to exercise is more effective than late exposure to exercise in enhancing cognitive capacity and reserve, or whether life-long exposure is needed. These experiments will utilize multiple experimental approaches (electrophysiological, immunohistochemical, biochemical, behavioral) to develop convergent evidence for the roles structural and functional changes play in optimizing cognitive capacity and cognitive reserve in the aging brain. ***The long-term objective of my research my research program will be to understand how exercise at different time points during development impacts different measures of brain plasticity in the male and female brain and how this relates to learning and memory processes across the lifespan. ***The short-term objectives specific to this research proposal are to: (1) determine whether early life experience is necessary for enhanced cognitive functioning in the aged brain, a way of indexing cognitive reserve; (2) determine whether increased activity in aged populations can have the same benefits, or (3) whether life-long exposure to exercise is required to optimize cognitive reserve. ***To examine these objectives we will employ several novel approaches that we propose can help us differentiate between cognitive capacity and cognitive reserve in the aged brain. Among these will be the introduction a modified rabies virus-mediated tracing system to examine the innervation of dentate granule cells in the aged brain, taking into account whether they were generated early in life (developmental neurogenesis) or later on in adulthood (adult neurogenesis). This will allow us to determine if enhanced neurogenesis early in life enhances cognitive reserve, and produces a population of neurons that can be used in the aged brain to enhance cognitive capacity on demand.

衰老的过程会对个体的认知能力产生负面影响，但个体之间存在显着的差异，其原因是辩论的主题。我们建议看看运动如何影响两个理论概念，认知能力和认知储备，在老年人的大脑。认知能力是一个术语，指的是我们如何学习，记忆和解决问题的机制，可以使用行为测试或电生理分析进行评估。认知储备用于描述优化或促进老年大脑神经弹性的因素，有助于促进更高水平的认知功能。有人提出，大脑结构的增加可能会增强认知储备。有大量证据表明，运动可以提高认知能力和认知储备，但运动益处的机制仍有待充分阐明。 在这些实验中，我们将确定早期锻炼是否比晚期锻炼更有效地增强认知能力和储备，或者是否需要终身锻炼。这些实验将利用多种实验方法（电生理学，免疫组织化学，生物化学，行为学）来开发结构和功能变化在优化衰老大脑中的认知能力和认知储备中所起作用的趋同证据。* 我的研究项目的长期目标是了解在发育过程中不同时间点的运动如何影响男性和女性大脑中大脑可塑性的不同测量，以及这与整个生命周期的学习和记忆过程的关系。* 本研究提案的短期目标是：（1）确定早期生活经验是否是增强老年大脑认知功能所必需的，这是一种索引认知储备的方法;（2）确定老年人群中增加活动是否具有相同的益处，或者（3）是否需要终身锻炼以优化认知储备。* 为了研究这些目标，我们将采用几种新的方法，我们提出这些方法可以帮助我们区分老年大脑中的认知能力和认知储备。其中将引入一种改良的狂犬病病毒介导的追踪系统，以检查老年大脑中齿状颗粒细胞的神经支配，同时考虑它们是在生命早期（发育神经发生）还是在成年后（成年神经发生）产生的。这将使我们能够确定生命早期增强的神经发生是否会增强认知储备，并产生一群可用于老年大脑的神经元，以根据需要增强认知能力。