Badea Alexandra, Mahzarnia Ali, Reddy Divya, Dong Zijian, Anderson Robert J, Moon Hae Sol, Stout Jacques A, Williams Janai, Hirschler Lydiane, Barbier Emmanuel L, Williams Christina L
Quantitative Imaging and Analysis Labs, Radiology Department, Duke University Medical Center, Durham, NC 27710, United States of America; Neurology Department, Duke University Medical Center, Durham, NC 27710, United States of America; Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC 27710, United States of America; Biomedical Engineering Department, Pratt School of Engineering, Duke University, Durham, NC 27710, United States of America.
Quantitative Imaging and Analysis Labs, Radiology Department, Duke University Medical Center, Durham, NC 27710, United States of America; Pediatrics Department, Stanford Medical School, Stanford, CA 94305, United States of America.
Magn Reson Imaging. 2025 Sep;121:110406. doi: 10.1016/j.mri.2025.110406. Epub 2025 May 3.
Exercise is a promising strategy for preventing or delaying Alzheimer's disease (AD), yet its mechanisms remain unclear. We investigated how exercise influences brain structure, function, and behavior in a familial AD model. Mice underwent voluntary, voluntary plus enforced exercise, or remained sedentary. Neuroimaging included in vivo manganese-enhanced MRI (MEMRI). perfusion, and ex vivo diffusion MRI to assess morphometry, activity, cerebral blood flow (CBF), microstructural integrity and connectivity. Both exercise regimens induced structural and functional brain adaptations while reducing anhedonia. Voluntary exercise increased cortical and limbic volumes, particularly in the hippocampus, cingulate, and entorhinal cortex, supporting cognitive and emotional regulation. Adding enforced exercise influenced subcortical and sensory regions, including visual, motor and associative areas, supporting sensory-motor integration. MEMRI revealed increased activity in sensorimotor, limbic, and associative cortices, with voluntary exercise enhancing limbic and associative regions, and enforced exercise strengthening sensorimotor and subcortical circuits. White matter integrity improved in memory-associate pathways such as the corpus callosum, cingulum, and hippocampal commissure. Synaptic remodeling was observed in the cingulate cortex, anterior thalamic nuclei, and amygdala. Voluntary exercise enhanced CBF in the motor cortex and hippocampus, while enforced exercise limited these increases. Connectivity analyses revealed exercise-responsive networks spanning the cingulate cortex, entorhinal cortex, anterior thalamic nuclei, and basolateral amygdala, and associated tracts. Graph analyses linked running distance with increased thalamic, brainstem, and cerebellar connectivity, associating exercise intensity with plasticity. These findings highlight the ability of chronic exercise to modulate neuroimaging biomarkers through distinct but complementary pathways, reinforcing its potential as a neuroprotective intervention for AD.
运动是预防或延缓阿尔茨海默病（AD）的一种很有前景的策略，但其机制仍不清楚。我们研究了运动如何影响家族性AD模型中的脑结构、功能和行为。小鼠进行自愿运动、自愿加强制运动或保持久坐不动。神经影像学检查包括体内锰增强磁共振成像（MEMRI）、灌注成像以及离体扩散磁共振成像，以评估形态学、活性、脑血流量（CBF）、微观结构完整性和连通性。两种运动方案都能诱导大脑结构和功能的适应性变化，同时减少快感缺失。自愿运动增加了皮质和边缘系统的体积，特别是在海马体、扣带回和内嗅皮质，有助于认知和情绪调节。增加强制运动则影响了皮质下和感觉区域，包括视觉、运动和联合区域，有助于感觉运动整合。MEMRI显示感觉运动、边缘和联合皮质的活性增加，自愿运动增强了边缘和联合区域，而强制运动则加强了感觉运动和皮质下回路。胼胝体、扣带束和海马连合等与记忆相关的通路中的白质完整性得到改善。在扣带回皮质、前丘脑核和杏仁核中观察到突触重塑。自愿运动增强了运动皮质和海马体的脑血流量，而强制运动则限制了这些增加。连通性分析揭示了跨越扣带回皮质、内嗅皮质、前丘脑核和基底外侧杏仁核以及相关神经束的运动反应网络。图谱分析将跑步距离与丘脑、脑干和小脑连通性的增加联系起来，将运动强度与可塑性联系起来。这些发现突出了长期运动通过不同但互补的途径调节神经影像学生物标志物的能力，强化了其作为AD神经保护干预措施的潜力。
