From Astrocyte Functions to Brain Dysfunctions: Brain “Stars” Take the Lead during Critical Periods of Early Postnatal Brain Development

Abstract

Astrocytes regulate the shape and functions of the synaptic and vascular compartments through modulatory membrane-bound proteins or released factors. Their peculiar position further allows them to form a functional unit that “senses” the brain state and secrete factors in the bloodstream as a reflection of this state. Imbalanced astrocyte activity can therefore have a drastic negative impact on the formation of neuronal synaptic networks and lead to the development of severe brain pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology and molecular make-up in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. The generation and differentiation/maturation of astrocytes (astrogenesis) occur during the critical period of early postnatal brain development. This is a time window of elevated astrocyte- and microglia-dependent synaptic phagocytosis (pruning), a process pivotal in refining neuronal networks. Therefore, any extrinsic and/or intrinsic cues altering this astrocyte-dependent synapse elimination during this critical period may result in altered synaptic remodeling and the onset of ND and NP disorders. Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling especially during early postnatal critical periods of brain development. We additionally propose alternative hypotheses to their putative involvement in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss sex-dependent effects on these neurodevelopmental processes.From a translational perspective, understanding age- and sex- dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease and may support the development of diagnostic tools or the selection of tailored treatment options for individual patients.