Microglial Biology and Physiology

Abstract

Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They originate from erythromyeloid progenitors (EMPs) in the yolk sac and develop in the forming CNS. Microglia serve as brain immune cells to orchestrate innate immune responses, however, they are distinct from other tissue macrophages due to their unique homeostatic phenotype and tight regulation by the CNS microenvironment. They exhibit multiple morphological phenotypes and functional profiles depending on their environment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. Alterations in microglia functionality are involved in brain aging, as well as in neurodegenerative diseases. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. One key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. Microglia execute varied tasks, not typical of those carried out by peripheral macrophages, which support optimal function of neurons and neuronal networks. Recent observations about microglia ontogeny combined with extensive gene expression profiling and emerged novel tools to study microglia biology allow us to characterize the variety of microglial phenotypes during development, homeostasis and disease.