Bridging acute and long-term exercise effects on brain function in older adults

 描述(申请人提供)：鉴于全球老年人比例的上升和大脑功能随着年龄的增长而逐渐下降，迫切需要开发新的干预措施来保护老化的大脑。实施运动训练以改善大脑功能的主要途径是增加心血管健康。然而，对于这种方法的有效性，人们的经验支持褒贬不一。此外，单次锻炼结束后一小时内的锻炼也会产生严重影响。这些影响发生在与健康相关的适应发生之前，动物研究表明，它们发生在受益于长期运动训练的相同大脑区域。因此，我们建议急性范式是一种工具，可以探索运动对这种早期、直接的反应，以确定如何最好地最大化运动训练对衰老大脑的长期好处。这就迫切需要确定运动对老化大脑的急性和长期影响之间的机制关系。我们的长期目标是确定运动如何保护大脑免受衰老的不利影响。反过来，我们在这项R21提案中的具体目标是支持或驳斥这样的概念，即一次运动会导致临床相关大脑网络的功能同步性急剧增加，这与同一大脑系统中累积的运动训练效果有关。我们的中心假设是，中等强度运动的效果将增加海马体与默认模式网络的功能同步性，以及前额叶皮质与Fronto-Execution网络的功能同步性，就像为期12周的中等强度运动训练计划一样。这一假说基于的数据表明，运动对与神经元可塑性和兴奋性相关的因素产生了急性影响，这些因素与运动对动物长期影响的大脑区域相同。这项拟议的研究的贡献是重大的，因为它将确定急性运动范式可以在多大程度上提供关于定期运动如何保护大脑免受衰老不利影响的洞察。这项拟议的研究是创新的，因为我们将第一次检查与急性和慢性运动相关的重叠神经系统和结果。总体而言，该项目的成功将使未来的研究能够研究不同的运动参数，如模式或强度，如何影响运动引起的大脑功能变化，这些影响的时间过程，以及与运动对老化大脑的直接影响相关的神经生物学机制。

 DESCRIPTION (provided by applicant): Given the rising proportion of older adults worldwide and the progressive decline in brain function with advancing age, there is a pressing need to develop novel interventions that protect the aging brain. The predominant approach for implementing exercise training to improve brain function is to increase cardiovascular fitness. However, there is mixed empirical support for the effectiveness of this approach. Further, there are also acute effects of exercise within one hour of the cessation of a single exercise session. These effects occur before adaptations related to fitness could occur and animal studies have shown they occur in the same brain regions that benefit from longer-term exercise training. Therefore, we propose the acute paradigm is a tool to probe this early, direct response from exercise in order to determine how best to maximize the long-term benefit of exercise training on the aging brain. This presents a critical need to determine the mechanistic relation between acute and long-term effects of exercise on the aging brain. Our long-term goal is to determine how exercise protects the brain from the adverse effects of aging. In turn, our specific objective in this R21 proposal is to support or refute the concept that a single session of exercise produces acute increases in functional synchrony of clinically relevant brain networks that are related to accrued exercise-training effects in the same brain systems. Our central hypothesis is that the effects of moderate intensity exercise will increase the functional synchrony of the hippocampus with the Default Mode Network, and the Prefrontal Cortex with the Fronto- Executive Network, in the same fashion as a 12-week moderate intensity exercise training program. This hypothesis is based on data showing acute effects of exercise on factors related to neuronal plasticity and excitability in the same brain regions that show long-term effects of exercise in animals. The contribution of the proposed research is significant because it will determine the extent to which the acute exercise paradigm can provide insight into how regular exercise protects the brain from adverse effects of aging. The proposed research is innovative because for the first time we will examine the overlapping neural systems and outcomes associated with acute and chronic exercise in the same individuals. Overall, success in this project will enable future research to study how varying exercise parameters such as mode or intensity affect exercise-induced change in brain function and the timecourse of these effects, as well as the neurobiological mechanisms associated with the direct effects of exercise on the aging brain.