Palasz Ewelina, Niewiadomski Wiktor, Gasiorowska Anna, Wysocka Adrianna, Stepniewska Anna, Niewiadomska Grazyna
Neurobiology Center, Nencki Institute of Experimental Biology, Polish Academy of Science, Warsaw, Poland.
Department of Applied Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Front Neurol. 2019 Nov 1;10:1143. doi: 10.3389/fneur.2019.01143. eCollection 2019.
Parkinson's disease (PD) is manifested by progressive motor, autonomic, and cognitive disturbances. Dopamine (DA) synthesizing neurons in the substantia nigra (SN) degenerate, causing a decline in DA level in the striatum that leads to the characteristic movement disorders. A disease-modifying therapy to arrest PD progression remains unattainable with current pharmacotherapies, most of which cause severe side effects and lose their efficacy with time. For this reason, there is a need to seek new therapies supporting the pharmacological treatment of PD. Motor therapy is recommended for pharmacologically treated PD patients as it alleviates the symptoms. Molecular mechanisms behind the beneficial effects of motor therapy are unknown, nor is it known whether such therapy may be neuroprotective in PD patients. Due to obvious limitations, human studies are unlikely to answer these questions; therefore, the use of animal models of PD seems indispensable. Motor therapy in animal models of PD characterized by the loss of dopaminergic neurons has neuroprotective and neuroregenerative effects, and the completeness of neuronal protection may depend on (i) degree of neuronal loss, (ii) duration and intensity of exercise, and (iii) time elapsed between insult and commencing of training. As the physical activity is neuroprotective for dopaminergic neurons, the question arises what is the mechanism of this protective action. A current hypothesis assumes a central role of neurotrophic factors in the neuroprotection of dopaminergic neurons, even though it is still not clear whether increased DA level in the nigrostriatal axis results from neurogenesis of dopaminergic neurons in the SN, recovery of the phenotype of dopaminergic neurons, increased sprouting of the residual dopaminergic axons in the striatum, or generation of local striatal neurons from inhibitory interneurons. In the present review, we discuss studies describing the influence of physical exercise on the PD-like changes manifested in animal models of the disease and focus our interest on the current state of knowledge on the mechanism of neuroprotection induced by physical activity as a supportive therapy in PD.
帕金森病（PD）表现为进行性运动、自主神经和认知功能障碍。黑质（SN）中合成多巴胺（DA）的神经元退化，导致纹状体中DA水平下降，进而引发特征性的运动障碍。目前的药物疗法仍无法实现阻止PD进展的疾病修饰治疗，其中大多数药物会引起严重的副作用，并且随着时间的推移会失去疗效。因此，需要寻求支持PD药物治疗的新疗法。运动疗法被推荐用于接受药物治疗的PD患者，因为它可以缓解症状。运动疗法有益效果背后的分子机制尚不清楚，也不清楚这种疗法对PD患者是否具有神经保护作用。由于存在明显的局限性，人体研究不太可能回答这些问题；因此，使用PD动物模型似乎是必不可少的。在以多巴胺能神经元丧失为特征的PD动物模型中，运动疗法具有神经保护和神经再生作用，神经元保护的完整性可能取决于：（i）神经元丧失的程度；（ii）运动的持续时间和强度；（iii）损伤与开始训练之间的时间间隔。由于体力活动对多巴胺能神经元具有神经保护作用，因此产生了这样一个问题：这种保护作用的机制是什么。目前的一种假设认为神经营养因子在多巴胺能神经元的神经保护中起核心作用，尽管目前尚不清楚黑质纹状体轴中DA水平的升高是源于SN中多巴胺能神经元的神经发生、多巴胺能神经元表型的恢复、纹状体中残留多巴胺能轴突的芽生增加，还是源于抑制性中间神经元产生局部纹状体神经元。在本综述中，我们讨论了描述体育锻炼对该疾病动物模型中表现出的PD样变化影响的研究，并将我们的兴趣集中在关于体力活动作为PD支持性治疗诱导神经保护机制的当前知识状态上。
