Fine-tuning the central nervous system: microglial modelling of cells and synapses

Abstract

Microglia constitute as much as 10-15% of all cells in the mammalian central nervous system (CNS) and are the only glial cells that do not arise from the neuroectoderm. As the principal CNS immune cells, microglial cells represent the first line of defence in response to exogenous threats. Past studies have largely been dedicated to defining the complex immune functions of microglial cells. However, our understanding of the roles of microglia has expanded radically over the past years. It is now clear that microglia are critically involved in shaping neural circuits in both the developing and adult CNS, and in modulating synaptic transmission in the adult brain. Intriguingly, microglial cells appear to use the same sets of tools, including cytokine and chemokine release as well as phagocytosis, whether modulating neural function or mediating the brain's innate immune responses. This review will discuss recent developments that have broadened our views of neuro-glial signalling to include the contribution of microglial cells.

eFORGE: A Tool for Identifying Cell Type-Specific Signal in Epigenomic Data

“…We then intersected the top 1,235 hypomethylated regions from the study that gave rise to the observed immune signal with the locations of active enhancers (n = 1,158) previously identified in microglial cells (Lavin et al., 2014). These immune cells constitute up to 15% of all cells in the mammalian CNS (Xavier et al., 2014). A Fisher’s exact test confirmed significant co-localization of the microglial-specific active enhancers (p value: 2.70e-07, odds ratio [OR]: 5.88, 95% confidence interval [CI]: 3.19–9.96), suggesting that microglial enhancers may be potential drivers of the MS EWAS signal.…”

The interplay between neurons and glia in synapse development and plasticity

“…Microglia and astrocytes eliminate synapses in a developmentally regulated and activity-dependent manner. The early postnatal pruning process by microglia is dependent upon the CX3CR1 receptor and complement receptor, CR3 [41,42]. New evidence also shows that microglia engulf synaptic material in the adult brain through a CR3-dependent process by binding to soluble β-amyloid oligomers [43].…”

Genes, circuits, and precision therapies for autism and related neurodevelopmental disorders

“…Astrocyte-specific restoration of Mecp2 in Mecp2 mutant mice restores function (101). Microglia also shape neuronal development and plasticity, and modulate synaptic transmission in the adult brain, via cytokine and chemokine release as well as phagocytosis (102, 103). Transplantation of wildtype microglia has been reported as reversing symptoms in a mouse model of Rett Syndrome, though the interpretation of these findings remains controversial (104, 105).…”