研究帕金森病啮齿动物模型中的情感神经精神症状。

International review of neurobiology Pub Date : 2024-01-01 Epub Date: 2023-09-15 DOI:10.1016/bs.irn.2023.08.006
Laura Boi, Gilberto Fisone
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摘要

抑郁、焦虑和冷漠等情感神经精神障碍是帕金森病(PD)患者最常见的非运动症状。这些症状通常出现在疾病的前驱期,一般认为是皮层中层结构的神经退行性过程所致,与黑质多巴胺能神经元的丧失同时发生。抑郁、焦虑和冷漠通常采用常规药物治疗,包括选择性血清素再摄取抑制剂、三环类抗抑郁药和多巴胺能激动剂。这些药物干预措施持续对抗帕金森病此类神经精神症状的能力仍然相对有限,因此开发可靠的实验模型是确定更有效治疗方法的重要工具。本章将介绍用于研究这些情感性神经精神症状的帕金森病啮齿动物模型。本章讨论了基于神经毒素的模型和遗传模型,以及用于识别抑郁和焦虑样行为、失乐症和冷漠的主要行为测试。此外,还综述了各种治疗方法抵消在不同模型中观察到的症状的能力。
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Investigating affective neuropsychiatric symptoms in rodent models of Parkinson's disease.

Affective neuropsychiatric disorders such as depression, anxiety and apathy are among the most frequent non-motor symptoms observed in people with Parkinson's disease (PD). These conditions often emerge during the prodromal phase of the disease and are generally considered to result from neurodegenerative processes in meso-corticolimbic structures, occurring in parallel to the loss of nigrostriatal dopaminergic neurons. Depression, anxiety, and apathy are often treated with conventional medications, including selective serotonin reuptake inhibitors, tricyclic antidepressants, and dopaminergic agonists. The ability of these pharmacological interventions to consistently counteract such neuropsychiatric symptoms in PD is still relatively limited and the development of reliable experimental models represents an important tool to identify more effective treatments. This chapter provides information on rodent models of PD utilized to study these affective neuropsychiatric symptoms. Neurotoxin-based and genetic models are discussed, together with the main behavioral tests utilized to identify depression- and anxiety-like behaviors, anhedonia, and apathy. The ability of various therapeutic approaches to counteract the symptoms observed in the various models is also reviewed.

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A general clinical overview of the non-motor symptoms in Parkinson's disease: Neuropsychiatric symptoms. Executive dysfunction and cognitive decline, a non-motor symptom of Parkinson's disease captured in animal models. Insight gained from using animal models to study pain in Parkinson's disease. Investigating affective neuropsychiatric symptoms in rodent models of Parkinson's disease. Macro and micro-sleep dysfunctions as translational biomarkers for Parkinson's disease.
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