Exercise Improves Cognitive Impairment and Dopamine Metabolism in MPTP-Treated Mice
Exercise Improves Cognitive Impairment and Dopamine Metabolism in MPTP-Treated Mice
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DOI：
10.1007/s12640-015-9566-4
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发表时间：
2016-01-01
影响因子：
3.7
通讯作者：
Prediger, Rui D.
中科院分区：
文献类型：
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作者：
Aguiar, Aderbal S., Jr.;Lopes, Samantha C.;Prediger, Rui D.
帕金森病 (PD) 的典型运动症状出现之前，会出现临床前阶段的非运动症状，包括认知障碍。目前PD的药物治疗是姑息性的，不能满足该疾病的临床挑战，如左旋多巴引起的运动障碍、非运动症状和神经保护。我们在 PD 临床前动物模型中研究了体育锻炼的神经保护和疾病缓解潜力。 C57BL/6 小鼠（成年雄性）在水平跑步机上跑步 6 周（中等强度，每周 5 次），并鼻内给予 65 mg/kg 神经毒素 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)。运动不能防止 MPTP 诱导的黑质纹状体神经变性或额纹状体多巴胺耗竭，但会减少纹状体多巴胺周转。运动还可以减轻 MPTP 治疗小鼠的程序性和工作记忆障碍以及 D-2 受体超敏反应。总之，运动改善了 PD 临床前动物模型的多巴胺能神经传递并增强了认知能力。
The classical motor symptoms of Parkinson's disease (PD) are preceded by non-motor symptoms in preclinical stages, including cognition impairment. The current drug treatment for PD is palliative and does not meet the clinical challenges of the disease, such as levodopa-induced dyskinesia, non-motor symptoms, and neuroprotection. We investigated the neuroprotective and disease-modifying potential of physical exercise in a preclinical animal model of PD. C57BL/6 mice (adult males) ran on a horizontal treadmill for 6 weeks (moderate intensity, 5 times/week) and were treated intranasally with 65 mg/kg of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Exercise did not protect against MPTP-induced nigrostriatal neurodegeneration or frontostriatal dopamine depletion but decreased striatal dopamine turnover. Exercise also attenuated procedural and working memory impairment and D-2 receptor hypersensitivity in MPTP-treated mice. In summary, exercise improved dopaminergic neurotransmission and enhanced cognition in a preclinical animal model of PD.