4.7 Review

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

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MDPI
DOI: 10.3390/ijms22094299

关键词

dopamine; nicotine; receptor; schizophrenia; Parkinson’ s disease; L-DOPA

资金

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [KRF-2020R1I1A3062151]

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The review discusses the interaction between the brain dopaminergic and cholinergic systems in the pathogenesis and treatment of schizophrenia and Parkinson's disease, including their roles in motor plan selection, negative symptoms, and nicotine-induced protection of DAergic neurons.
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 alpha 7 nicotinic cholinergic receptor and the dopamine D-1 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.

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