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脑胆碱能和多巴胺能系统功能相互作用在精神分裂症和帕金森病发病机制和治疗中的作用。

Roles of the Functional Interaction between Brain Cholinergic and Dopaminergic Systems in the Pathogenesis and Treatment of Schizophrenia and Parkinson's Disease.

机构信息

Pharmacology Laboratory, College of Pharmacy, Chonnam National University, Gwang-Ju 61186, Korea.

Department of Pathology, College of Medicine, University of South Alabama, Mobile, AL 36617, USA.

出版信息

Int J Mol Sci. 2021 Apr 21;22(9):4299. doi: 10.3390/ijms22094299.

Abstract

Most physiologic processes in the brain and related diseases involve more than one neurotransmitter system. Thus, elucidation of the interaction between different neurotransmitter systems could allow for better therapeutic approaches to the treatments of related diseases. Dopaminergic (DAergic) and cholinergic neurotransmitter system regulate various brain functions that include cognition, movement, emotion, etc. This review focuses on the interaction between the brain DAergic and cholinergic systems with respect to the pathogenesis and treatment of schizophrenia and Parkinson's disease (PD). We first discussed the selection of motor plans at the level of basal ganglia, the major DAergic and cholinergic pathways in the brain, and the receptor subtypes involved in the interaction between the two signaling systems. Next, the roles of each signaling system were discussed in the context of the negative symptoms of schizophrenia, with a focus on the α7 nicotinic cholinergic receptor and the dopamine D receptor in the prefrontal cortex. In addition, the roles of the nicotinic and dopamine receptors were discussed in the context of regulation of striatal cholinergic interneurons, which play crucial roles in the degeneration of nigrostriatal DAergic neurons and the development of L-DOPA-induced dyskinesia in PD patients. Finally, we discussed the general mechanisms of nicotine-induced protection of DAergic neurons.

摘要

大多数大脑的生理过程和相关疾病涉及多个神经递质系统。因此,阐明不同神经递质系统之间的相互作用,可以为相关疾病的治疗提供更好的治疗方法。多巴胺能(DAergic)和胆碱能神经递质系统调节包括认知、运动、情绪等在内的各种大脑功能。这篇综述重点介绍了大脑 DAergic 和胆碱能系统之间的相互作用,涉及精神分裂症和帕金森病(PD)的发病机制和治疗。我们首先讨论了在基底神经节水平上选择运动计划的问题,讨论了大脑中主要的 DAergic 和胆碱能途径,以及涉及两个信号系统相互作用的受体亚型。接下来,我们讨论了每个信号系统在精神分裂症阴性症状中的作用,重点讨论了前额叶皮层中的α7 烟碱型乙酰胆碱受体和多巴胺 D 受体。此外,我们还讨论了烟碱和多巴胺受体在纹状体胆碱能中间神经元调节中的作用,这些神经元在黑质纹状体 DAergic 神经元变性和 PD 患者中左旋多巴诱导的运动障碍的发展中起着至关重要的作用。最后,我们讨论了尼古丁诱导的 DAergic 神经元保护的一般机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d2d/8122651/75b09257a27e/ijms-22-04299-g001.jpg

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