College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.
Arch Pharm Res. 2018 Oct;41(10):943-954. doi: 10.1007/s12272-018-1063-x. Epub 2018 Aug 22.
Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by motor dysfunction, including bradykinesia, tremor, rigidity, and postural instability. Recent clinical findings recognize PD as a complex disease with diverse neuropsychiatric complications. Depression is the most frequent non-motor psychiatric symptom experienced in PD, and it is associated with poor quality of life. While the pathophysiology of PD-associated depression is not directly related to neurodegenerative processes in the substantia nigra, underlying mechanisms remain unclear and there are few symptomatic treatments. Altered adult hippocampal neurogenesis is considered crucial for the development and treatment of depression. In genetic animal models and human postmortem studies of PD, severely impaired adult neurogenesis has been observed, with patients showing hippocampal atrophy and disrupted hippocampal neurogenesis. Because adult newborn neurons appear to exert various functions, which relate to non-motor symptoms observed in PD, there might be a close correlation between malformation of newborn neurons in the adult hippocampus and depressive symptoms. Here, we discuss current concepts regarding impaired hippocampal neurogenesis and non-motor symptoms of PD, and review PD-associated pathophysiological factors regulating neurogenesis, including inflammatory signaling and autophagy. We present a novel framework for targeting adult hippocampal neurogenesis, which could provide a promising treatment for PD-associated depression.
帕金森病（PD）是一种常见的进行性神经退行性疾病，其特征为运动功能障碍，包括运动迟缓、震颤、僵硬和姿势不稳。最近的临床发现认为 PD 是一种复杂的疾病，伴有多种神经精神并发症。抑郁症是 PD 患者最常见的非运动性精神症状之一，它与生活质量差有关。虽然 PD 相关抑郁的病理生理学与黑质中的神经退行性过程没有直接关系，但潜在机制仍不清楚，且对症治疗方法很少。成年海马神经发生的改变被认为对抑郁症的发展和治疗至关重要。在遗传动物模型和 PD 的人类尸检研究中，观察到严重受损的成年神经发生，患者表现出海马萎缩和海马神经发生中断。由于成年新生神经元似乎具有各种功能，这些功能与 PD 中观察到的非运动症状有关，因此成年海马中新神经元的畸形与抑郁症状之间可能存在密切关联。在这里，我们讨论了目前关于海马神经发生受损和 PD 的非运动症状的概念，并回顾了调节神经发生的 PD 相关病理生理因素，包括炎症信号和自噬。我们提出了一个针对成年海马神经发生的新框架，这可能为 PD 相关抑郁提供一种有前途的治疗方法。
