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

• Published in: Neurobiology of disease 2019-12, Vol.132, p.104586-104586, Article 104586
• Main Authors: Xu, Liping, Long, Jingyi, Su, Zhongqiang, Xu, Benke, Lin, Michael, Chen, Yuncai, Long, Dahong
• Format: Article
• Language: English
• Subjects: Aging; Cholinergic cells; Hippocampus; Memory; Physical training; Presynaptic terminals; Synaptophysin
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2019.104586

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. •Voluntary daily running for 5 months improves spatial memory in old C57 mice.•Running prevents age-related loss of synaptophysin in hippocampal CA1 and DG.•Running prevents selective loss of cholinergic inputs in the aged hippocampus.•Enhanced memory relies on the numbers of presynaptic puncta and cholinergic inputs.