Department of Exercise Prescription, Kon-Yang University, 119 Daehangro, Nonsan city, Chungnam 320-711, Republic of Korea.
Neurosci Res. 2011 Feb;69(2):161-73. doi: 10.1016/j.neures.2010.10.004. Epub 2010 Oct 20.
The present study was undertaken to further investigate the protective effect of treadmill exercise on the hippocampal proteins associated with neuronal cell death in an aged transgenic (Tg) mice with Alzheimer's disease (AD). To address this, Tg mouse model of AD, Tg-NSE/PS2m, which expresses human mutant PS2 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. The exercised mice were treadmill run at speed of 12 m/min, 60 min/day, 5 days/week on a 0% gradient for 3 months. Treadmill exercised mice improved cognitive function in water maze test. Treadmill exercised mice significantly reduced the expression of Aβ-42, Cox-2, and caspase-3 in the hippocampus. In parallel, treadmill exercised Tg mice decreased the phosphorylation levels of JNK, p38MAPK and tau (Ser404, Ser202, Thr231), and increased the phosphorylation levels of ERK, PI3K, Akt and GSK-3α/β. In addition, treadmill exercised Tg mice up-regulated the expressions of NGF, BDNF and phospho-CREB, and the expressions of SOD-1, SOD-2 and HSP-70. Treadmill exercised Tg mice up-regulated the expression of Bcl-2, and down-regulated the expressions of cytochrome c and Bax in the hippocampus. The number of TUNEL-positive cells in the hippocampus in mice was significantly decreased after treadmill exercise. Finally, serum TC, insulin, glucose, and corticosterone levels were significantly decreased in the Tg mice after treadmill exercise. As a consequence of such change, Aβ-dependent neuronal cell death in the hippocampus of Tg mice was markedly suppressed following treadmill exercise. These results strongly suggest that treadmill exercise provides a therapeutic potential to inhibit both Aβ-42 and neuronal death pathways. Therefore, treadmill exercise may be beneficial in prevention or treatment of AD.
本研究旨在进一步探讨跑步机运动对阿尔茨海默病（AD）转基因（Tg）小鼠海马神经元细胞死亡相关蛋白的保护作用。为此，选择了表达脑中人类突变 PS2 的 Tg-NSE/PS2m AD 小鼠模型。动物从 24 个月龄开始进行 12 周的跑步机运动。运动组的小鼠以 12m/min 的速度在跑步机上跑，每天 60min，每周 5 天，坡度为 0%，持续 3 个月。跑步机运动的小鼠在水迷宫测试中改善了认知功能。跑步机运动的 Tg 小鼠显著降低了海马中 Aβ-42、Cox-2 和 caspase-3 的表达。平行地，跑步机运动的 Tg 小鼠降低了 JNK、p38MAPK 和 tau（Ser404、Ser202、Thr231）的磷酸化水平，增加了 ERK、PI3K、Akt 和 GSK-3α/β 的磷酸化水平。此外，跑步机运动的 Tg 小鼠上调了 NGF、BDNF 和磷酸化 CREB 的表达，以及 SOD-1、SOD-2 和 HSP-70 的表达。跑步机运动的 Tg 小鼠上调了 Bcl-2 的表达，下调了海马中细胞色素 c 和 Bax 的表达。跑步机运动后，小鼠海马中 TUNEL 阳性细胞的数量明显减少。最后，跑步机运动后 Tg 小鼠的血清 TC、胰岛素、血糖和皮质酮水平显著降低。因此，Aβ 依赖性神经元细胞死亡在 Tg 小鼠的海马中明显受到抑制。这些结果强烈表明，跑步机运动为抑制 Aβ-42 和神经元死亡途径提供了治疗潜力。因此，跑步机运动可能对 AD 的预防或治疗有益。
