Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease.
Running wheel exercise reduces α-synuclein aggregation and improves motor and cognitive function in a transgenic mouse model of Parkinson's disease.
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DOI：
10.1371/journal.pone.0190160
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Freed CR
中科院分区：
文献类型：
--
作者：
Zhou W;Barkow JC;Freed CR
运动已被推荐用于改善帕金森病患者的运动功能，但其在改变疾病进展方面的价值尚不清楚。在这项研究中，我们检测了跑轮运动对小鼠的神经保护作用。在成年野生型小鼠中，一周的跑轮活动导致肌肉和血浆中DJ - 1蛋白浓度显著增加。在DJ - 1基因敲除小鼠中，跑轮表现慢得多，转棒（Rotarod）表现也降低，这表明DJ - 1蛋白是正常运动活动所必需的。为了观察运动是否能预防在所有神经元中表达人突变型α - 突触核蛋白的转基因动物的异常蛋白质沉积和行为衰退，我们在12个月大的有症状前动物的笼子里设置了跑轮。对其活动进行了为期3个月的监测。3个月后，与跑轮锁定的对照转基因动物相比，运动的动物在转棒和莫里斯水迷宫中的运动和认知表现明显更好。生化分析显示，与对照小鼠相比，运动的小鼠大脑中DJ - 1、热休克蛋白70（Hsp70）和脑源性神经营养因子（BDNF）浓度显著更高，α - 突触核蛋白聚集明显更少。相比之下，与对照小鼠相比，运动小鼠的血浆α - 突触核蛋白浓度显著更高。我们的研究结果表明，运动可能通过防止大脑中异常蛋白质聚集来减缓帕金森病的进展。
Exercise has been recommended to improve motor function in Parkinson patients, but its value in altering progression of disease is unknown. In this study, we examined the neuroprotective effects of running wheel exercise in mice. In adult wild-type mice, one week of running wheel activity led to significantly increased DJ-1 protein concentrations in muscle and plasma. In DJ-1 knockout mice, running wheel performance was much slower and Rotarod performance was reduced, suggesting that DJ-1 protein is required for normal motor activity. To see if exercise can prevent abnormal protein deposition and behavioral decline in transgenic animals expressing a mutant human form of α-synuclein in all neurons, we set up running wheels in the cages of pre-symptomatic animals at 12 months old. Activity was monitored for a 3-month period. After 3 months, motor and cognitive performance on the Rotarod and Morris Water Maze were significantly better in running animals compared to control transgenic animals with locked running wheels. Biochemical analysis revealed that running mice had significantly higher DJ-1, Hsp70 and BDNF concentrations and had significantly less α-synuclein aggregation in brain compared to control mice. By contrast, plasma concentrations of α-synuclein were significantly higher in exercising mice compared to control mice. Our results suggest that exercise may slow the progression of Parkinson’s disease by preventing abnormal protein aggregation in brain.
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