Relevance of interactions between dopamine and glutamate neurotransmission in schizophrenia.
Relevance of interactions between dopamine and glutamate neurotransmission in schizophrenia.
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DOI：
10.1038/s41380-022-01649-w
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发表时间：
2022-09
影响因子：
11
通讯作者：
Freyberg, Zachary
中科院分区：
文献类型：
--
作者：
Buck, Silas A.;Erickson-Oberg, M. Quincy;Logan, Ryan W.;Freyberg, Zachary
多巴胺（DA）和谷氨酸的神经传递强烈地牵连在精神分裂症的病理生理。虽然大多数研究都集中在只释放DA或谷氨酸的神经元的贡献上，但单独的DA和谷氨酸模型都不能概括精神分裂症的全部病理生理学。类似地，仅限于任一系统的治疗策略不能有效地治疗精神分裂症的所有三个主要症状领域：阳性、阴性和认知症状。越来越多的证据表明DA和谷氨酸系统之间存在广泛的相互作用，因此更有效的治疗可能需要靶向DA和谷氨酸信号传导。这提供了一种可能性，即破坏这两个系统之间的DA-谷氨酸回路，特别是在纹状体和前脑中，最终导致精神分裂症的病理生理学。然而，这些相互作用背后的机制及其对精神分裂症的贡献仍不清楚。除了仅释放DA或谷氨酸的神经元之间的回路或系统水平的相互作用之外，在这里，我们认为涉及共同释放DA和谷氨酸的神经元亚群的功能改变提供了DA和谷氨酸系统之间的新整合点，为我们理解精神分裂症病理生理学提供了关键的缺失环节。因此，更好地了解DA/谷氨酸从这些神经元共同释放的机制可能会为精神分裂症的病理生理学提供新的线索，并导致更有效的治疗方法。
Dopamine (DA) and glutamate neurotransmission are strongly implicated in schizophrenia pathophysiology. While most studies focus on contributions of neurons that release only DA or glutamate, neither DA nor glutamate models alone recapitulate the full spectrum of schizophrenia pathophysiology. Similarly, therapeutic strategies limited to either system cannot effectively treat all three major symptom domains of schizophrenia: positive, negative, and cognitive symptoms. Increasing evidence suggests extensive interactions between the DA and glutamate system and more effective treatments may therefore require the targeting of both DA and glutamate signaling. This offers the possibility that disrupting DA-glutamate circuitry between these two systems, particularly in the striatum and forebrain, culminate in schizophrenia pathophysiology. Yet, the mechanisms behind these interactions and their contributions to schizophrenia remain unclear. In addition to circuit- or system-level interactions between neurons that solely release either DA or glutamate, here we posit that functional alterations involving a subpopulation of neurons that co-release both DA and glutamate provide a novel point of integration between DA and glutamate systems, offering a key missing link in our understanding of schizophrenia pathophysiology. Better understanding of mechanisms underlying DA/glutamate co-release from these neurons may therefore shed new light on schizophrenia pathophysiology and lead to more effective therapeutics.
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