FORce-Mediated Cognition by Exercise (FORCE)

定期的有氧运动，如每天快走40分钟，有助于保持认知健康，即使在生命的后期也是如此。随着年龄的增长，海马体--大脑中与记忆和学习有关的部分--的体积会减少。锻炼不仅可以防止这种体积的减少，还可以增加新的神经元和其他脑细胞的体积。通过锻炼肌肉释放的生物化学物质可能支持这种增长。但它们如何影响海马细胞仍然是个谜。该项目支持试图通过考虑一种变革性的新范式来解开这个谜团的研究，在这种范式中，运动过程中的肌肉收缩被传导到海马细胞本身的收缩。这项研究的结果可能导致病理的逆向工程，例如阿尔茨海默病、抑郁症和焦虑，导致海马体的大小和功能缩小。该项目基于这样的假设，即锻炼肌肉会使海马细胞收缩，这种收缩能力会导致脑干细胞产生新的神经元。这一假设是基于PI实验室的初步发现。这一假说将通过训练培养在培养皿中的小鼠肌肉组织来检验。运动肌肉组织释放的生物化学物质将被提供给从培养皿中培养的小鼠脑中提取的小鼠海马细胞。运动对脑细胞的影响将通过测量脑细胞的收缩能力和培养皿上新神经元的形成来评估。这一假说还将在跑步和久坐的小鼠身上进行验证，方法是量化已知的与细胞收缩有关的大脑蛋白质的相对表达。这项研究的结果将通过(1)向不同的老年人展示运动大脑；(2)为社交媒体开发关于运动大脑互动的5部分视频系列；(3)让高中生和本科生参与运动大脑研究；以及(4)在当地图书馆、校园开放日、农贸市场和当地学校发表演讲。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Regular aerobic exercise, such as fast walking 40 minutes per day, helps maintain cognitive health, even at late stages of life. With ageing, the volume of the hippocampus- part of the brain attributed to memory and learning, decreases. Exercise not only prevents this loss in volume, but increases the volume due to new neurons, and other brain cell. Biochemicals released by exercising muscle likely support this growth. But how they influence hippocampal cells remains a mystery. This project supports research that attempts to resolve this enigma by considering a transformative new paradigm wherein muscle contraction during exercise is transduced to contraction of hippocampal cells themselves. The results from the study may lead to reverse-engineering of pathologies, such as e.g., Alzheimer’s disease, depression, and anxiety that result in a diminished size and function of the hippocampus. The project is based on the hypothesis that exercising muscle makes hippocampal cells contractile, and that this contractility results in new neurons from brain stem cells. The hypothesis is based on preliminary findings in the PIs’ labs. The hypothesis will be tested by exercising mouse muscle tissue cultured on a petri dish. The biochemicals released by the exercising muscle tissue will be provided to mouse hippocampal cells extracted from mouse brain cultured on a dish. The effect of exercise on brain cells will be evaluated by measuring brain cell contractility and formation of new neurons on the dish. The hypothesis will also be tested in running and sedentary mice by quantifying relative expressions of brain proteins known to be responsible for cell contractility. The results of the study will be disseminated to the public through (1) exercise-brain presentations to diverse elderly populations; (2) development of a 5-part video series on exercise-brain interactions for social media; (3) Involvement of high school and undergraduate students in the exercise-brain research; and (4) presentations at the local library, campus open house, farmers market and local schools.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.