ASTROGLIA: Molecular Mechanisms, Functional Roles, and Neurophysiological Implications in the Central Nervous System

Abstract

Astrocytes, the principal components of astroglia, play essential roles in maintaining neuronal and synaptic homeostasis in the central nervous system. By regulating extracellular levels of glutamate, potassium (K+), and calcium (Ca2+), they prevent excitotoxicity and support neuronal survival. Astrocytes also modulate synaptic transmission and plasticity through gliotransmission, including vesicular glutamate release and D-serine synthesis via the serine shuttle, which regulates NMDA receptor activity. They provide metabolic support by facilitating glucose and oxygen transport from the vasculature, forming dynamic neurovascular units. Through signaling pathways such as cAMP-PKA and interactions with neurotrophic factors like BDNF and GDNF, astrocytes influence gene expression, synaptic remodeling, and plasticity. Furthermore, astrocytes exhibit regional and functional heterogeneity, which underlies their diverse contributions to both physiological and pathological conditions, including neurodegenerative diseases. This review summarizes current knowledge on astrocytic regulation of neuronal homeostasis, synaptic plasticity, and metabolism, highlighting their mechanisms of network communication, gliotransmission, and regional specialization, and discusses their implications in health and disease.