Titova Nataliya, Schapira Anthony H V, Chaudhuri K Ray, Qamar Mubasher A, Katunina Elena, Jenner Peter
Federal State Budgetary Educational Institution of Higher Education "N.I. Pirogov Russian National Research Medical University" of the Ministry of Healthcare of the Russian Federation, Moscow, Russia.
UCL Institute of Neurology, London, United Kingdom.
Int Rev Neurobiol. 2017;133:63-89. doi: 10.1016/bs.irn.2017.05.018. Epub 2017 Jul 10.
Nonmotor symptoms of Parkinson's disease (PD) range from neuropsychiatric, cognitive to sleep and sensory disorders and can arise from the disease process as well as from drug treatment. The clinical heterogeneity of nonmotor symptoms of PD is underpinned by a wide range of neuropathological and molecular pathology, affecting almost the entire range of neurotransmitters present in brain and the periphery. Understanding the neurobiology and pathology of nonmotor symptoms is crucial to the effective treatment of PD and currently a key unmet need. This bench-to-bedside translational concept can only be successful if robust animal models of PD charting the genesis and natural history of nonmotor symptoms can be devised. Toxin-based and transgenic rodent and primate models of PD have given us important clues to the underlying basis of motor symptomatology and in addition, can provide a snapshot of some nonmotor aspects of PD, although the data are far from complete. In this chapter, we discuss some of the nonmotor aspects of the available experimental models of PD and how the development of robust animal models to understand and treat nonmotor symptoms needs to become a research priority.
帕金森病（PD）的非运动症状涵盖神经精神、认知、睡眠及感觉障碍等方面，可由疾病进程以及药物治疗引发。PD非运动症状的临床异质性有多种神经病理学和分子病理学基础，几乎影响到大脑和外周存在的所有神经递质。了解非运动症状的神经生物学和病理学对于PD的有效治疗至关重要，而目前这是一个关键的未满足需求。只有设计出能够描绘非运动症状发生和自然史的可靠的PD动物模型，这种从实验台到病床的转化概念才可能成功。基于毒素的以及转基因的啮齿动物和灵长类动物PD模型为我们提供了运动症状学潜在基础的重要线索，此外，尽管数据远不完整，但它们也能提供PD一些非运动方面的简要情况。在本章中，我们将讨论现有PD实验模型的一些非运动方面，以及如何将开发可靠的动物模型以理解和治疗非运动症状作为研究重点。
