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恢复的突触前突触素和胆碱能输入有助于体育锻炼对老年小鼠空间记忆的保护作用。

Restored presynaptic synaptophysin and cholinergic inputs contribute to the protective effects of physical running on spatial memory in aged mice.

机构信息

Key Lab of Neuroscience, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, China.

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 511436, China.

出版信息

Neurobiol Dis. 2019 Dec;132:104586. doi: 10.1016/j.nbd.2019.104586. Epub 2019 Aug 27.

DOI:10.1016/j.nbd.2019.104586
PMID:31470103
Abstract

The effects of prolonged physical training on memory performance and underlying presynaptic mechanisms were investigated in old C57BL/6 mice. Training via voluntary running wheels was initiated at 16 months of age and continued for 5 months (1 h per day, 5 days per week), followed by testing of learning and memory functions and counting of presynaptic puncta and cholinergic inputs in the hippocampus. Trained old mice were compared to their age-matched sedentary controls and adult controls. This training strategy improved hippocampal-dependent spatial memory function tested via a novel location task, and enhanced memory was accompanied by restored presynaptic puncta and cholinergic fibers in area CA1 and DG of the hippocampus in old mice. Particularly, the training selectively affected presynaptic vesicle protein synaptophysin but not growth associated protein GAP-43, and the increased number of synaptophysin puncta positively correlates with improved memory performance. To better understand the neurochemical mechanisms by which prolonged physical training protects against aging-related memory deficits, the cholinergic inputs to the hippocampus were compared among the three groups of mice and correlated with memory performance. While the running prevented age-related loss of cholinergic inputs, it has limited impact on the projection source cells in the medial septum-diagonal band (MS-DB). Importantly, cholinergic fibers in area CA1 and DG positively correlated with spatial memory function. These data suggest that the preservation of presynaptic inputs, particularly those involved in the integrity of memory performance, contributes critically to the beneficial effects of physical running initiated at an older age.

摘要

研究了长期体育锻炼对记忆表现和潜在的突触前机制的影响,对象是老年 C57BL/6 小鼠。16 个月大时开始通过自愿跑步轮进行训练,持续 5 个月(每天 1 小时,每周 5 天),然后测试学习和记忆功能,并计数海马中的突触前突和胆碱能输入。将训练过的老年小鼠与同龄久坐不动的对照组和成年对照组进行比较。这种训练策略改善了通过新位置任务测试的海马依赖性空间记忆功能,并且记忆增强伴随着海马 CA1 和 DG 区突触前突和胆碱能纤维的恢复。特别是,训练选择性地影响突触小泡蛋白突触素而不是生长相关蛋白 GAP-43 的数量,并且突触素突的数量增加与记忆表现的改善呈正相关。为了更好地理解长期体育锻炼保护免受与年龄相关的记忆缺陷的神经化学机制,比较了三组小鼠的海马胆碱能输入,并与记忆表现相关联。虽然跑步防止了与年龄相关的胆碱能输入的丧失,但它对中隔-斜角带(MS-DB)中的投射源细胞的影响有限。重要的是,CA1 和 DG 区的胆碱能纤维与空间记忆功能呈正相关。这些数据表明,突触前输入的保存,特别是那些与记忆表现的完整性有关的输入的保存,对老年时开始的体育锻炼的有益效果至关重要。

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