长期自愿运动后阿尔茨海默病 APP 基因敲入小鼠模型对大脑病理学、焦虑和认知功能的显著影响。

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

机构信息

Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Dr W, Lethbridge, AB, T1K 3M4, Canada.

Present address: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, 63110, USA.

出版信息

Alzheimers Res Ther. 2022 Sep 30;14(1):143. doi: 10.1186/s13195-022-01085-6.

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 APP mice were exposed to long-term voluntary exercise.

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 APP mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APP 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 APP 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.

CONCLUSION

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

背景

积极的生活方式与老年人认知功能的改善有关，并且可能预防或减缓包括阿尔茨海默病（AD）在内的各种神经退行性疾病的进展。为了研究这些保护作用，将雄性 APP 小鼠暴露于长期的自愿运动中。

方法

将 3 个月大的 AD 小鼠饲养在笼子中，笼子中补充有一个跑步轮，以进行 9 个月的长期运动。在 12 个月大时，对所有组完成行为测试。完成行为测试后，评估其大脑中的淀粉样蛋白病理、小胶质细胞和胆碱能细胞。

结果

结果表明，允许自愿运动的 APP 小鼠的认知功能得到改善。此外，长期运动还改善了 APP 小鼠的焦虑，这可以通过测量 Morris 水迷宫中的触须探索来评估。我们还发现，在允许在其笼中进行运动的 APP 小鼠的大脑中，淀粉样蛋白负荷和小胶质细胞减少，并且胆碱能细胞得到保留。与 AD 相关的这些大脑病理学的深刻减少可能是广泛和定期运动后观察到的学习和记忆功能改善的原因。