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帕金森病啮齿动物模型中运动和非运动障碍的行为分析。

Behavioral analysis of motor and non-motor impairment in rodent models of Parkinson's disease.

作者信息

Sheta Razan, Bérard Morgan, Musiol Dylan, Martínez-Drudis Laura, Oueslati Abid

机构信息

CHU de Québec-Université Laval Research Center, Neuroscience Axis, Québec City, QC, Canada.

Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec City, QC, Canada.

出版信息

Front Aging Neurosci. 2024 Dec 23;16:1464706. doi: 10.3389/fnagi.2024.1464706. eCollection 2024.

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the degeneration of dopamine neurons in the substantia nigra pars compacta, leading to motor and non-motor symptoms. While motor symptoms such as rigidity, tremor, bradykinesia/akinesia, and postural instability are well-recognized, non-motor symptoms including cognitive decline, depression, and anxiety also significantly impact patients' quality of life. Preclinical research utilizing animal models has been instrumental in understanding PD pathophysiology and exploring therapeutic interventions. Various approaches, including genetic manipulations and toxin-induced insults, aim to recapitulate both motor and non-motor aspects of PD in animal models. However, no single model fully replicates the complex spectrum of PD symptoms. Behavioral assessments play a crucial role in evaluating motor impairments in PD animal models, focusing on the manifestation of Parkinsonian motor phenotype. These assessments encompass locomotor activities, motor behavior abnormalities, and induced rotational behavior. Similarly, non-motor features are assessed through tests evaluating behavioral alterations such as depression, anxiety, and cognitive impairment. Although numerous animal models of PD have been developed, including non-human primates and both mammalian and non-mammalian species, this review focuses on motor and non-motor testing methodologies in rodent models, which are the most commonly used. Emphasizing genetic and toxin-induced PD models in mice and rats, we highlight key testing strategies and the significance of each method in addressing specific research questions and interpreting experimental data. By providing a comprehensive overview of these testing approaches, this review aims to advance understanding and foster progress in PD research.

摘要

帕金森病(PD)是一种常见的神经退行性疾病,其特征是黑质致密部多巴胺能神经元变性,导致运动和非运动症状。虽然诸如僵硬、震颤、运动迟缓/运动不能和姿势不稳等运动症状广为人知,但包括认知衰退、抑郁和焦虑在内的非运动症状也会显著影响患者的生活质量。利用动物模型进行的临床前研究有助于理解帕金森病的病理生理学并探索治疗干预措施。包括基因操作和毒素诱导损伤在内的各种方法旨在在动物模型中重现帕金森病的运动和非运动方面。然而,没有单一模型能完全复制帕金森病症状的复杂谱系。行为评估在评估帕金森病动物模型的运动损伤中起着关键作用,重点关注帕金森运动表型的表现。这些评估包括运动活动、运动行为异常和诱导旋转行为。同样,通过评估抑郁、焦虑和认知障碍等行为改变的测试来评估非运动特征。尽管已经开发了许多帕金森病动物模型,包括非人类灵长类动物以及哺乳动物和非哺乳动物物种,但本综述重点关注啮齿动物模型中的运动和非运动测试方法,啮齿动物模型是最常用的。我们强调小鼠和大鼠中基因和毒素诱导的帕金森病模型,突出关键测试策略以及每种方法在解决特定研究问题和解释实验数据方面的重要性。通过全面概述这些测试方法,本综述旨在促进对帕金森病研究的理解并推动其进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd4f/11701160/cd871a18ae98/fnagi-16-1464706-g0001.jpg

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