Université Lille-Nord de France, UDSL, F-59000 Lille, France.
Neurobiol Dis. 2011 Aug;43(2):486-94. doi: 10.1016/j.nbd.2011.04.022. Epub 2011 May 4.
Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences.
tau 病理学存在于许多神经退行性疾病中，这些疾病被称为 tau 病，包括阿尔茨海默病。身体活动是影响记忆和突触可塑性的关键过程的生活方式因素。长期自愿运动是否对 Tau 病理学及其病理生理后果有影响目前尚不清楚。为了解决这个问题，我们研究了长期自愿运动对 THY-Tau22 转基因阿尔茨海默病样 Tau 病理学模型的影响，该模型的特点是 Tau 病理学、胆碱能改变和随后的记忆损伤逐渐发展。将 3 个月大的 THY-Tau22 小鼠和野生型同窝仔鼠分配到标准饲养或补充跑步轮的饲养中。经过 9 个月的运动后，对小鼠进行记忆表现评估，并检查海马 Tau 病理学、胆碱能缺陷、炎症和与胆固醇代谢相关的基因。运动可预防 THY-Tau22 小鼠的记忆改变。这伴随着海马 Tau 病理学的减少和内侧隔胆碱乙酰转移酶表达的丧失得到预防。虽然大多数与胆固醇相关的基因在跑步 THY-Tau22 小鼠的海马体中的表达保持不变，但我们观察到 NPC1 和 NPC2 的 mRNA 水平显著上调，这些基因参与胆固醇从溶酶体中的转运。我们的数据支持这样一种观点，即长期自愿的体育锻炼是一种有效的策略，能够减轻 Tau 病理学及其病理生理后果。
