Astrocytes as central integrators of neural circuit function: Mechanisms and dysregulation in neuropsychiatric disorders

Abstract

Background: Astrocytes, far beyond passive support cells, are critical regulators in brain homeostasis, intricately regulating synaptic plasticity, neurovascular integrity, metabolic support, and neuroimmune communication. Their dysregulation is increasingly implicated in the pathophysiology of a wide range of neuropsychiatric and neurodegenerative diseases.

Methods: This review synthesizes fundamental research exploring how astrocytic reactivity disrupts homeostatic functions. It evaluates current mechanisms of astrocyte-mediated circuit dysfunction, specifically focusing on tripartite synapse and the secretion of immunomodulatory factors. The analysis further explores the utility of emerging technologies, including single-cell transcriptomics and in vivo astrocyte-specific manipulation tools.

Results: The synthesis identifies that astrocytic reactivity leads to a profound disruption of the glutamate/GABA balance, contributing to impaired synaptic signaling. A central finding is that altered astrocyte–neuron–microglia crosstalk contributes to circuit dysfunction. Furthermore, A significant challenge remains in the characterization of heterogeneous, context-dependent astrocyte states and their specific contributions to pathogenesis.

Conclusion: A deeper mechanistic understanding of astrocyte biology is paramount for unveiling novel disease aetiologies and unlocking the potential for innovative astrocyte-targeted therapeutic strategies.

Keywords

astrocytes / glutamate/GABA homeostasis / neuroinflammation / neuropsychiatric disorders / therapeutic targets / tripartite synapse

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