Department of Nursing, Jinju Health College, Jinju, 52655, Republic of Korea.
Department of Neuropsychiatry, Graduate School of Oriental Medicine, Dongguk University, Gyeongju, 38066, Republic of Korea.
Mol Neurobiol. 2019 May;56(5):3069-3078. doi: 10.1007/s12035-018-1239-x. Epub 2018 Aug 8.
Exercise increases the levels of neurogenic factors and enhances neurogenesis, memory, and learning. However, the molecular link between exercise and neurogenesis is not clear. The purpose of this study was to examine the effects of exercise intensity on cognitive function and protein expression in the hippocampus of old mice. To compare the effects of aerobic exercise intensity on cognition in old mice, we exposed 18-month-old mice to low- and moderate-intensity treadmill exercise for 4 weeks. Moderate-intensity exercise improved cognitive function in the old mice, while low-intensity exercise did not. To investigate the underlying mechanisms, two-dimensional electrophoresis was used to examine protein expression. Using peptide fingerprinting mass spectrometry, we identified 19 proteins that were upregulated in the hippocampus following exercise training, and seven of these proteins were normalized by the control value. Among them, the levels of 14-3-3 zeta and heat shock protein 70, which have been shown to be induced by exercise training and related to neurogenesis, were dramatically increased by moderate exercise. Hippocalcin, α-spectrin, ovarian tumor domain-containing ubiquitin aldehyde-binding protein 1 (otub1), mu-crystallin, serine racemase, and rho GDP dissociation inhibitor 1, which are related to neurogenesis, neuroprotection, and synaptic strength, were upregulated in the hippocampus by moderate exercise. In addition, we confirmed that neurogenic markers, including doublecortin and the neuronal nuclei antigen, and hippocalcin, otub1, and spectrin-α are potential molecular links between hippocampal neurogenesis and exercise in the elderly. Thus, these results showed that steady moderate-intensity exercise delayed the declines in cognitive function in the elderly through the activation of multiple factors.
运动能增加神经营养因子的水平，促进神经发生、记忆和学习。然而，运动与神经发生之间的分子联系尚不清楚。本研究的目的是探讨运动强度对老年小鼠海马认知功能和蛋白质表达的影响。为了比较有氧运动强度对老年小鼠认知能力的影响，我们让 18 月龄的小鼠进行 4 周的低强度和中等强度的跑步机运动。中等强度运动改善了老年小鼠的认知功能，而低强度运动则没有。为了探讨潜在的机制，我们使用二维电泳来检测蛋白质表达。使用肽指纹图谱质谱法，我们鉴定了运动训练后海马中上调的 19 种蛋白质，其中 7 种蛋白质的表达水平用对照值归一化。在这些蛋白质中，14-3-3 ζ和热休克蛋白 70 的水平显著增加，这两种蛋白质已被证明可被运动训练诱导，与神经发生有关。中等强度运动还显著增加了海马中的钙调蛋白、α- spectrin、卵巢肿瘤结构域包含泛素醛结合蛋白 1（otub1）、μ-晶状体蛋白、丝氨酸 racemase 和 rho GDP 解离抑制剂 1，这些蛋白质与神经发生、神经保护和突触强度有关。此外，我们还证实，神经发生标志物，包括双皮质蛋白和神经元核抗原，以及钙调蛋白、otub1 和 spectrin-α 是海马神经发生和老年人运动之间的潜在分子联系。因此，这些结果表明，稳定的中等强度运动通过激活多种因素延缓了老年人认知功能的下降。
