Immune cells and CNS physiology: Microglia and beyond

Abstract

Recent advances have directed our knowledge of the immune system from a narrative of “self” versus “nonself” to one in which immune function is critical for homeostasis of organs throughout the body. This is also the case with respect to the central nervous system (CNS). CNS immunity exists in a segregated state, with a marked partition occurring between the brain parenchyma and meningeal spaces. While the brain parenchyma is patrolled by perivascular macrophages and microglia, the meningeal spaces are supplied with a diverse immune repertoire. In this review, we posit that such partition allows for neuro–immune crosstalk to be properly tuned. Convention may imply that meningeal immunity is an ominous threat to brain function; however, recent studies have shown that its presence may instead be a steady hand directing the CNS to optimal performance.

MAPK signaling determines lysophosphatidic acid (LPA)-induced inflammation in microglia

“…Microglia are the predominant type of immune cells in the central nervous system (CNS) that comprise approximately 5-12% of glial cells [1,2]. Microglia derive from mesodermal progenitors that arise from the yolk sac and colonize the neuroepithelium by day E9.5 [3].…”

Microglial cell‐derived interleukin‐6 influences behavior and inflammatory response in the brain following traumatic brain injury

“…Once established, microglia are distinguished by their longevity and self-renewal character, while other mononuclear phagocytic cells, including circulating monocytes, peripheral mononuclear phagocytes and myeloid progenitors in the bone marrow, have a limited life span (Ransohoff & Cardona, 2010). In resting conditions, microglia present a ramified morphology and play an array of functions, including clearance of dead cells (Norris & Kipnis, 2018) and control of neuronal communication (Kattenmann, Kirchhoff, & Verhratsky, 2013). In contrast, after a homeostatic disturbance such as TBI, microglia acquire a phagocytic phenotype and increase the production of IL-6 (Chhor et al, 2017;Lee et al, 1993;Loane & Kumar, 2016).…”

Post-SSRI Sexual Dysfunction: A Bioelectric Mechanism?

“…102 Such alterations can plausibly affect neural (and non-neural) responses such as could be important for human sexual function, either directly on somatic cells or through indirect effects acting through the microbiome, immune system, or brain. 12,[103][104][105] Bioelectric memory has not yet been demonstrated in human patient tissues, representing an important area for subsequent work, which could be addressed in vivo and in human organoid systems in vitro. 106 Paralleling the development of ion channel modulator drug cocktails, guided by computational models of bioelectric circuits to induce desired pro-regenerative states, it's possible that the negative effects of SSRI exposure could someday be mitigated by rationally designed cocktails of already humanapproved drugs acting as ionoceuticals.…”