Abstract
Localisation of mast cells (MCs) at the abluminal side of blood vessels in the brain favours their interaction with glial cells, neurons, and endothelial cells, resulting in the activation of these cells and the release of pro-inflammatory mediators. In turn, stimulation of glial cells, such as microglia, astrocytes, and oligodendrocytes may result in the modulation of MC activities. MCs, microglia, astrocytes, and oligodendrocytes all express P2X receptors (P2XRs) family members that are selectively engaged by ATP. As increased concentrations of extracellular adenosine 5′-triphosphate (ATP) are present in the brain in neuropathological conditions, P2XR activation in MCs and glial cells contributes to the control of their communication and amplification of the inflammatory response. In this review we discuss P2XR-mediated MC activation, its bi-directional effect on microglia, astrocytes and oligodendrocytes and role in neuroinflammation.
Highlights
Mast cells (MCs) are immune cells that form part of the innate branch of the immune system
It appears that P2X4 in rat cultured microglia is predominantly stored intracellularly while membrane expression is rapidly upregulated through C-C chemokine receptor type (CCR) 2-mediated activation upon CCL2 or CCL12 ligand binding [112]
Upregulation of P2X7 expression in microglia was observed in SOD1 mice [122] and receptor activation was found to modulate autophagic flux, a homeostatic mechanism involved in degradation of damaged organelles and protein aggregates, whose abnormalities were reported in amyotrophic lateral sclerosis (ASL) [123]
Summary
Mast cells (MCs) are immune cells that form part of the innate branch of the immune system. A first wave of MCs originates during embryonic development from yolk-sac progenitors followed by a second wave of bone marrow-derived MCs in adulthood. This duality in the origin of MCs may influence the cell phenotype and function in various tissues [4,5]. The number of MCs in the brain can be sex-dependent, especially in young mice pups, where the total number of MCs in the preoptic area is nearly two times higher for males than females, potentially contributing to the gender bias in human neuropathology for diseases such as autism spectrum disorder (ASD) or schizophrenia [13,14]. We explore the effects of the P2XR-mediated MC activation on microglia, astrocytes and oligodendrocytes and its role in neuroinflammation
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