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

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.