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超越神经元:多巴胺信号如何影响星形胶质细胞的功能和病理生理学?

Beyond neurons: How does dopamine signaling impact astrocytic functions and pathophysiology?

作者信息

Favetta Giulia, Bubacco Luigi

机构信息

Department of Biology, University of Padova, Padova, Italy.

Department of Biology, University of Padova, Padova, Italy; Centro Studi per la Neurodegenerazione (CESNE), University of Padova, Padova, Italy.

出版信息

Prog Neurobiol. 2025 Aug;251:102798. doi: 10.1016/j.pneurobio.2025.102798. Epub 2025 Jun 19.

Abstract

Astrocytes, the most abundant glial cells in the central nervous system (CNS), are critical regulators of brain homeostasis and play an active role in synaptic signaling and plasticity. While dopamine, a key catecholamine neurotransmitter, has been traditionally associated with neuronal functions, emerging evidence highlights its significant impact on astrocytic physiology. This review explores how astrocytes contribute to dopaminergic signaling and the implications of this interaction in both physiological and pathological contexts. Specifically, we examined astrocytic dopamine receptor expression, signaling mechanisms, and region-specific effects on neuroinflammation, synaptic regulation, and neurotrophic factor secretion. Notably, astrocytic dopamine receptor activation plays dual inflammatory roles, modulating both anti- and pro- inflammatory responses depending on the receptor subtype and pathological environment. Furthermore, dopamine-evoked gliotransmitter release and neurotrophin secretion highlight the role of astrocytes in astrocyte-to-neuron communication, which impacts synaptic plasticity and neuronal survival. Dysfunction of astrocytic dopaminergic signaling has been implicated in neurodegenerative diseases such as Parkinson's disease, where dopamine depletion drives reactive astrogliosis, altered glutamate homeostasis, and inflammatory responses. These findings underscore the complexity of astrocytic responses to dopamine and their potential as targets in conditions characterized by dysregulation of dopaminergic signaling. By highlighting recent advancements in understanding dopamine-astrocyte interactions, this review aims to provide insights into the broader roles of astrocytes in dopaminergic systems and their therapeutic potential in CNS disorders.

摘要

星形胶质细胞是中枢神经系统(CNS)中数量最多的神经胶质细胞,是脑内稳态的关键调节因子,在突触信号传导和可塑性方面发挥着积极作用。虽然多巴胺作为一种关键的儿茶酚胺神经递质,传统上一直与神经元功能相关,但新出现的证据凸显了其对星形胶质细胞生理学的重大影响。本综述探讨了星形胶质细胞如何促进多巴胺能信号传导,以及这种相互作用在生理和病理情况下的意义。具体而言,我们研究了星形胶质细胞多巴胺受体的表达、信号传导机制以及对神经炎症、突触调节和神经营养因子分泌的区域特异性影响。值得注意的是,星形胶质细胞多巴胺受体的激活具有双重炎症作用,根据受体亚型和病理环境调节抗炎和促炎反应。此外,多巴胺诱发的胶质递质释放和神经营养因子分泌突出了星形胶质细胞在星形胶质细胞与神经元通讯中的作用,这会影响突触可塑性和神经元存活。星形胶质细胞多巴胺能信号传导功能障碍与帕金森病等神经退行性疾病有关,在帕金森病中,多巴胺耗竭会导致反应性星形胶质细胞增生、谷氨酸稳态改变和炎症反应。这些发现强调了星形胶质细胞对多巴胺反应的复杂性及其作为多巴胺能信号失调相关病症靶点的潜力。通过强调在理解多巴胺 - 星形胶质细胞相互作用方面的最新进展,本综述旨在深入了解星形胶质细胞在多巴胺能系统中的更广泛作用及其在中枢神经系统疾病中的治疗潜力。

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