Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice.
Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice.
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DOI：
10.1186/1750-1326-9-54
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发表时间：
2014-11-28
影响因子：
15.1
通讯作者：
Eriksen JL
中科院分区：
文献类型：
--
作者：
Ohia-Nwoko O;Montazari S;Lau YS;Eriksen JL
最近的流行病学证据表明，通过增加身体活动来改变生活方式可能是改善阿尔茨海默病和其他牛头病症状和减缓疾病进展的一种非药物方法。先前的研究表明，运动可以减少tau蛋白的过度磷酸化，然而，尚不清楚运动是否可以减少可溶性或不可溶性tau蛋白聚集体和神经原纤维缠结的积累，这两者都是神经退行性tau病的神经病理学标志。在这项研究中，7月龄的P301S tau转基因小鼠进行了12周的强制跑步运动，并在10月龄时评估其运动功能和tau病理的影响。运动改善了一般运动和探索活动，并导致脊髓和海马中全长和过度磷酸化的tau蛋白显著减少，以及脊髓中萨科齐不溶性AT8-tau蛋白的减少。运动并没有减轻海马或皮层中显著的神经元损失。研究人员还测量了参与自噬的关键蛋白——微管相关蛋白1A/1B轻链3和p62/sequestosome 1——以评估自噬是否与运动诱导的tau蛋白聚集减少有关。强迫跑步机运动对P301S小鼠自噬蛋白水平无显著影响。我们的研究结果表明，强迫跑步机运动对老年P301S tau小鼠的大脑和脊髓有不同的影响，对脊髓的影响大于对大脑的影响。我们的工作增加了越来越多的证据，证明运动对牛头病有益，然而这些好处在疾病的后期可能更加有限。
Recent epidemiological evidence suggests that modifying lifestyle by increasing physical activity could be a non-pharmacological approach to improving symptoms and slowing disease progression in Alzheimer’s disease and other tauopathies. Previous studies have shown that exercise reduces tau hyperphosphorylation, however, it is not known whether exercise reduces the accumulation of soluble or insoluble tau aggregates and neurofibrillary tangles, which are both neuropathological hallmarks of neurodegenerative tauopathy. In this study, 7-month old P301S tau transgenic mice were subjected to 12-weeks of forced treadmill exercise and evaluated for effects on motor function and tau pathology at 10 months of age. Exercise improved general locomotor and exploratory activity and resulted in significant reductions in full-length and hyperphosphorylated tau in the spinal cord and hippocampus as well as a reduction in sarkosyl-insoluble AT8-tau in the spinal cord. Exercise did not attenuate significant neuron loss in the hippocampus or cortex. Key proteins involved in autophagy—microtubule-associated protein 1A/1B light chain 3 and p62/sequestosome 1 —were also measured to assess whether autophagy is implicated in the exercised-induced reduction of aggregated tau protein. There were no significant effects of forced treadmill exercise on autophagy protein levels in P301S mice. Our results suggest that forced treadmill exercise differently affects the brain and spinal cord of aged P301S tau mice, with greater benefits observed in the spinal cord versus the brain. Our work adds to the growing body of evidence that exercise is beneficial in tauopathy, however these benefits may be more limited at later stages of disease.
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影响因子：
2.1
作者：
Dao AT;Zagaar MA;Levine AT;Salim S;Eriksen JL;Alkadhi KA
通讯作者：
Alkadhi KA
影响因子：
3.3
作者：
Al-Jarrah, M.;Pothakos, K.;Lau, Y.-S.
通讯作者：
Lau, Y.-S.
影响因子：
4.7
作者：
Babu, JR;Geetha, T;Wooten, MW
通讯作者：
Wooten, MW
影响因子：
5.3
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
DOI：
10.1097/00005072-199906000-00011
发表时间：
1999-06-01
影响因子：
3.2
作者：
Bugiani, O;Murrell, JR;Ghetti, B
通讯作者：
Ghetti, B