Long-term treadmill exercise attenuates tau pathology in P301S tau transgenic mice

Molecular Neurodegeneration

Jason L Eriksen²  Yuen-Sum Lau¹  Saghi Montazari²  Odochi Ohia-Nwoko² 

[1] American Association of Colleges of Pharmacy, Alexandria, VA 22314, USA;Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 521 Science and Research Building 2, 4800 Calhoun Road, Houston, TX 77204, USA

关键词: Neurodegeneration;    Alzheimer’s disease;    Exercise;    Tau pathology;   

Others  :  1138624
DOI  :  10.1186/1750-1326-9-54

 received in 2014-04-22, accepted in 2014-11-17,  发布年份 2014

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2014 Ohia-Nwoko et al.; licensee BioMed Central Ltd.

【 图 表 】

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