Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise

长期自愿锻炼对阿尔茨海默病敲入型 APPNL-GF 小鼠模型的脑病理、焦虑和认知功能产生显著影响

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作者:Jogender Mehla, Scott H Deibel, Hadil Karem, Shakhawat Hossain, Sean G Lacoursiere, Robert J Sutherland, Majid H Mohajerani #, Robert J McDonald #

Background

An active lifestyle is associated with improved cognitive functions in aged people and may prevent or slow down the progression of various neurodegenerative diseases including Alzheimer's disease (AD). To investigate these protective effects, male APPNL-G-F mice were exposed to long-term voluntary exercise.

Conclusion

These findings suggest the potential of physical exercise to mitigate the cognitive deficits in AD.

Methods

Three-month-old AD mice were housed in a cage supplemented with a running wheel for 9 months for long-term exercise. At the age of 12 months, behavioral tests were completed for all groups. After completing behavioral testing, their brains were assessed for amyloid pathology, microgliosis, and cholinergic cells.

Results

The results showed that APPNL-G-F mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APPNL-G-F mice as assessed by measuring thigmotaxis in the Morris water task. We also found reductions in amyloid load and microgliosis, and a preservation of cholinergic cells in the brain of APPNL-G-F mice allowed to exercise in their home cages. These profound reductions in brain pathology associated with AD are likely responsible for the observed improvement of learning and memory functions following extensive and regular exercise.

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