Microglia roles in synaptic plasticity and myelination in homeostatic conditions and neurodevelopmental disorders

Abstract

Microglia are the immune cells of the brain, involved in synapse formation, circuit sculpting, myelination, plasticity, and cognition. Being active players during early development as well as in adulthood, microglia affect other cells directly by their long processes and unique receptors and indirectly by secreting growth factors and cytokines. In this review, we discuss the roles of microglia in neurodevelopmental disorders, synaptic plasticity, myelination, and homeostatic conditions throughout human and mouse development. Within these processes, we specifically focus on the contribution of altered microglial interactions with neurons and oligodendrocytes, altered cytokine and growth factor activities, and alterations in the complement system. We conclude by highlighting future perspectives and providing an overview of future research on microglia.

Essential omega-3 fatty acids tune microglial phagocytosis of synaptic elements in the developing brain

“…The phagocytic activity of microglia during development is crucial in shaping neuronal networks, and dysfunction of this activity contributes to neurodevelopmental disorders 26,[58][59][60][61] .…”

“…Deficits in microglia-mediated synaptic refinement lead to dysfunctional neuronal networks and behavioral abnormalities resembling some aspects of neurodevelopmental disorders 26,[58][59][60][61] . Here, we show that n-3 PUFA deficient microglia display an altered homeostatic molecular profile at weaning with features similar to neurodegenerative microglia, previously reported as more phagocytic 92 .…”

The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

“…The exchange of signals linking microglia with neurons is required for the maintenance of housekeeping functions and homeostasis within the CNS. This communication is crucial in brain functions, including angiogenesis [ 1 ], axonal outgrowth [ 2 ], development [ 3 ], neurogenesis [ 4 ], neuronal circuit remodelling [ 5 ], plasticity [ 6 , 7 ] and immune responses [ 8 ]. As a consequence, it translates into the proper functioning of the organism at cognitive, emotional and behavioural levels.…”

Myelin Plasticity and Repair: Neuro-Glial Choir Sets the Tuning

“…In homeostatic condition, microglia can support survival, differentiation, myelinogenesis, and homeostasis of the oligodendroglial lineage (Hamilton and Rome, 1994;Butovsky et al, 2006;Pasquini et al, 2011;Shigemoto-Mogami et al, 2014;Hagemeyer et al, 2017;Wlodarczyk et al, 2017 ; Figure 2). Activated microglia associated with myelin deficits has further been described in neurodevelopmental disorders and mental conditions (Garey, 2010;Morgan et al, 2010;Janova et al, 2018;Bar and Barak, 2019;Barak et al, 2019). These defects might be partly related to a lack of adaptive myelination.…”

“…The crosstalk between neuron and glia is complex and probably critical when it comes to myelination regulation, in adaptive processes and repair. Astrocytes and microglial cells are known to participate in (re)myelination modulation and have been described to detect neuronal activity (for review, Domingues et al, 2016;Adaikkan and Tsai, 2019;Bar and Barak, 2019;Molina-Gonzalez and Miron, 2019). Although astrocytes and microglia may be involved in molecular mechanisms modulating adaptive myelination, the understanding of their impact on adult myelination processes is still limited.…”