The Indispensable Roles of Microglia and Astrocytes during Brain Development

Abstract

Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same developmental processes such as neuro-/gliogenesis, angiogenesis, axonal outgrowth, synaptogenesis and synaptic pruning. Due to their important instructive roles in these processes, dysfunction of microglia or astrocytes during brain development could contribute to neurodevelopmental disorders and potentially even late-onset neuropathology. A better understanding of the origin, differentiation process and developmental functions of microglia and astrocytes will help to fully appreciate their role both in the developing as well as in the adult brain, in health and disease.

Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia

“…Throughout late embryogenesis and early postnatal periods, these progenitors and their progeny exhibit a predominantly amoeboid morphology and are clustered in “hotspots” near the pial surface, the subventricular zone, the subplate, and in the developing hippocampus and white matter tracts, where they are believed to contribute to axon outgrowth, development of the vasculature, and regulation of neural progenitor and neuron viability (Reemst et al, 2016). Little is known about the subsequent transition from these immature phenotypes to the highly branched morphologies and tiled distributions of adult microglia.…”

“…Nonetheless, gene expression analyses and immunohistochemical studies suggest the presence of heterogeneity within the mature microglial population (Lawson et al, 1990; de Haas et al, 2008; Sharaf et al, 2013; Yang et al, 2013; Grabert et al, 2016). Limited information is available about deep brain microglia, such as those that populate the basal ganglia (BG), and dorsal-ventral differences in phenotype analogous to those observed in other glial cell populations have not been reported (Ginhoux et al, 2013; Zuchero and Barres, 2015; Reemst et al, 2016). …”

Sculpting Cerebral Cortex with Serotonin in Rodent and Primate

“…Astrocytes are the largest glial population in the mammalian brain and are well-known to 'feed neurons' by transforming glucose into lactate that neurons can directly use as 'carburant', to scavenge debris and to regulate neural transmission and ionic homeostasis of the brain [61,62]. Microglial cells play a role of sentinels of inflammatory state of the brain.…”

“…In addition to these roles, astrocytes and microglial cells participate in regulating cell proliferation, neuronal migration and plasticity (for review, see Refs. [6,61,63]). Oligodendrocytes myelinate axons and increase their conduction velocity (they will not be further described in this chapter).…”

“…[61]). These cells bear several 5-HT receptors depending on their stage and state (resting or activated) making 5-HT an indirect actor of cortical development via the modulation of their functions [170].…”