Abstract
Astrocytes are essential players in brain circuit development and homeostasis, controlling many aspects of synapse formation, function, plasticity and elimination both during development and adulthood. Accordingly, alterations in astrocyte morphogenesis and physiology may severely affect proper brain development, causing neurological or neuropsychiatric conditions. Recent findings revealed a huge astrocyte heterogeneity among different brain areas, which is likely at the foundation of the different synaptogenic potential of these cells in selected brain regions. This review highlights recent findings on novel mechanisms that regulate astrocyte-mediated synaptogenesis during development, and the control of synapse number in the critical period or upon synaptic plasticity.
Highlights
Humanitas Clinical and Research Center—IRCCS—NeuroCenter, via Manzoni 56, 20089 Rozzano, Milan, CNR, Department of Biomedical Sciences, Institute of Neuroscience—URT Humanitas, via Manzoni 56, 20089 Rozzano, Italy
It has been recently demonstrated that, concomitantly to TSP secretion, astrocytes release the innate immune molecule pentraxin3 (PTX3), which promotes the functional maturation of excitatory synapses formed during the first wave of synaptogenesis by inducing AMPA receptors’ clustering at the synapse [29]
In the developing mouse brain, Hevin and secreted protein acidic and rich in cysteine (SPARC) are expressed at high levels in astrocytes during the second and third weeks, which coincide with periods of synapse and neuroligin-1B [17]
Summary
The synaptogenic role of astrocytes was initially discovered using a purified retinal ganglion cell (RGC) culture system. RGC neurons grown in the absence of astroglia form very few synapses. Synapse formation is increased upon the addition of astrocyte-conditioned media (ACM) [13]. A large number of studies demonstrated that astrocytes are essential players in promoting synaptogenesis, during brain development, and provided evidence for many astrocyte-secreted factors, including proteins, lipids and small molecules that control different aspects of excitatory and inhibitory synapse formation and maturation (Table 1)
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