The "molecular soldiers" of the CNS: Astrocytes, a comprehensive review on their roles and molecular signatures

Abstract

For a long time, neurons held the position of central players in the nervous system. Since there are far more astrocytes than neurons in the brain, it makes us wonder if these cells just take up space and support the neurons or if they are actively participating in central nervous system (CNS) homeostasis. Now, astrocytes' contribution to CNS physiology is appreciated as they are known to regulate ion and neurotransmitter levels, synapse formation and elimination, blood-brain barrier integrity, immune function, cerebral blood flow, and many more. In many neurological and psychiatric disorders, astrocyte functions are altered. Advancements in microscopic and transcriptomic tools revealed populations of astrocytes with varied morphology, electrophysiological properties, and transcriptomic profiles. Neuron-circuit-specific functions and neuron-specific interactions of astroglial subpopulations are found, which suggests that diversity is essential in carrying out diverse region-specific CNS functions. Investigations on heterogeneous astrocyte populations are revealing new astrocyte functions and their role in pathological conditions, opening a new therapeutic avenue for targeting neurological conditions. The true extent of astrocytic heterogeneity and its functional implications are yet to be fully explored. This review summarizes essential astrocytic functions and their relevance in pathological conditions and discusses astrocytic diversity in relation to morphology, function, and gene expression throughout the CNS.

Keywords: A1/A2 variant; Heterogeneity; Neurodegeneration; Neuroinflammation; Synaptic plasticity.