Sublime Microglia: Expanding Roles for the Guardians of the CNS

Abstract

Recent findings challenge the concept that microglia solely function in disease states in the central nervous system (CNS). Rather than simply reacting to CNS injury, infection, or pathology, emerging lines of evidence indicate that microglia sculpt the structure of the CNS, refine neuronal circuitry and network connectivity, and contribute to plasticity. These physiological functions of microglia in the normal CNS begin during development and persist into maturity. Here, we develop a conceptual framework for functions of microglia beyond neuroinflammation and discuss the rich repertoire of signaling and communication motifs in microglia that are critical both in pathology and for the normal physiology of the CNS.

Glial and Neuroimmune Mechanisms as Critical Modulators of Drug Use and Abuse

“…Microglia and astrocytes have received considerable attention recently due to their contributions to a wide array of homeostatic and non-inflammatory processes, as well as during states of heightened inflammation and injury (Brown and Neher, 2014;Ginhoux and Jung, 2014;Prinz and Priller, 2014;Salter and Beggs, 2014;Walsh et al, 2014). Glial and neuroimmune mechanisms have been extensively characterized in the context of pathological pain (Grace et al, 2014a), while researchers attempting to decode the complex etiology of neurodegenerative disorders such as Alzheimer's disease have also argued for a more holistic framework, where the interactions and compensatory responses between neurons, glia, and vascular cells all contribute to the progression of the disease (De Strooper and Karran, 2016).…”

“…Glial cells, including microglia and astrocytes, are also influenced by exposure to abused drugs, and their responses likely contribute to the behavioral outcomes associated with substance abuse (Coller and Hutchinson, 2012;Miguel-Hidalgo, 2009). Once viewed as passive support elements for neurons, it is now clear that both microglia and astrocytes can actively regulate many aspects of neuronal function, including neurotransmitter release, gene regulation, electrophysiology, dendritic morphology, synaptic connectivity, and cell viability (Araque et al, 2014;Eroglu and Barres, 2010;Kettenmann et al, 2013;Salter and Beggs, 2014). As immunocompetent sentinels of the central nervous system (CNS), they are also critical participants in the development and protection of the CNS, including neural development, cell migration, programmed cell death, and regulation of synapse maturation and elimination Chung et al, 2015a;Hanisch and Kettenmann, 2007;.…”

Microglia and Monocyte-Derived Macrophages in Stroke

“…In the resting state, resident microglia constantly monitor the surroundings. The microglial surveillance maintains hemostasis in the developing and adult CNS by controlling the number of synapse and neuronal firings and remove debris [43,44].…”

Antagonizing peroxisome proliferator‐activated receptor γ facilitates M1‐to‐M2 shift of microglia by enhancing autophagy via the LKB1–AMPK signaling pathway

“…Neuroinflammation is triggered by activated and proliferating microglial cells, astrocytes, and other myeloid cells that ultimately produce pro‐inflammatory cytokines, chemokines, and other inflammatory mediators, leading to neuronal damage (Ullah et al., 2017; White, Lawrence, Brough & Rivers‐Auty, 2017). Microglial cells play critical roles in immune surveillance and host defense by acting as the prime resident innate‐immune cells in the central nervous system (CNS; Perry & Holmes, 2014; Salter & Beggs, 2014). Under normal conditions, microglial cells not only provide surveillance of the CNS environment but also respond to danger signals (Crotti & Ransohoff, 2016; Perry & Teeling, 2013).…”