Genotypic/phenotypic mediators of synaptic plasticity in aging

衰老过程中突触可塑性的基因型/表型介质

• 批准号: 435808-2013
• 负责人: DeBeaumont, Louis
• 金额: $ 2.11万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=631392
• 关键词: Genotypic; phenotypic; mediators; synaptic; plasticity

Considerable research efforts are invested to shed some light on the mechanisms underlying cognitive function changes associated with age, particularly those pertaining to premature memory and learning decline. Impaired synaptic plasticity in age-susceptible brain regions was found to best predict cognitive decline in aging. Until recently, inferences about neuronal plasticity in humans could only be drawn from indirect measures of plasticity, such as cognitive function changes. The recent development of non-invasive brain stimulation techniques, however, provides a variety of research tools allowing the direct assessment of synaptic plasticity mechanisms in human cortical areas. Work from our group has shown that synaptic plasticity, as assessed with these brain stimulation techniques, are significantly linked with changes in functionally related brain functions. One of the major interests in using these innovative brain stimulation techniques resides in their proven capacity to generate durable brain plasticity improvements. Perhaps most importantly, these long-term after-effects were shown to be associated with lasting behavioural benefits. The work that will be conducted in the proposed research program will take advantage of the latest and most advanced brain stimulation techniques to noninvasively probe plasticity mechanisms underlying functional decline as people age. In addition to its significant contribution to knowledge advancement, intervention protocols aiming to restore brain plasticity in the aging population may also prove to be protective in people at risk of developing age-related neurodegenerative conditions such as Alzheimer's disease.

人们投入了大量的研究努力，以阐明与年龄相关的认知功能变化的潜在机制，特别是与早熟记忆和学习能力下降有关的机制。研究发现，年龄敏感的大脑区域的突触可塑性受损最能预测老年人的认知能力下降。直到最近，关于人类神经元可塑性的推断只能从认知功能变化等间接可塑性指标中得出。然而，非侵入性脑刺激技术的最新发展提供了各种研究工具，使得直接评估人类皮质区域的突触可塑性机制成为可能。我们小组的工作表明，用这些脑刺激技术评估的突触可塑性与功能相关的大脑功能的变化显著相关。使用这些创新的脑刺激技术的主要兴趣之一在于它们被证明有能力产生持久的大脑可塑性改善。也许最重要的是，这些长期的后遗症被证明与持久的行为益处有关。拟议的研究计划中将进行的工作将利用最新和最先进的脑刺激技术，以非侵入性的方式探索随着年龄增长而导致功能衰退的可塑性机制。除了对知识进步的重大贡献外，旨在恢复老龄化人口大脑可塑性的干预方案也可能被证明对患有阿尔茨海默病等与年龄相关的神经退行性疾病的风险人群具有保护作用。