Microglia activation in central nervous system disorders: A review of recent mechanistic investigations and development efforts

Abstract

Microglia are the principal resident immune cells in the central nervous system (CNS) and play important roles in the development of CNS disorders. In recent years, there have been significant developments in our understanding of microglia, and we now have greater insight into the temporal and spatial patterns of microglia activation in a variety of CNS disorders, as well as the interactions between microglia and neurons. A variety of signaling pathways have been implicated. However, to date, all published clinical trials have failed to demonstrate efficacy over placebo. This review summarizes the results of recent important studies and attempts to provide a mechanistic view of microglia activation, inflammation, tissue repair, and CNS disorders.

SARS-CoV-2 neurotropism-induced anxiety/depression-like behaviors require Microglia activation

“…This observation indicates a direct involvement of microglia in the development of abnormal neuronal activity in response to SARS-CoV-2 infection. The observed neuronal activity rescue upon microglial inhibition aligns with previous studies showing that microglial activation is a key driver of neuronal activity changes in various CNS disorders (67). Understanding the interactions between microglia and neurons and how SARS-CoV-2 infection influences these processes in the amygdala is crucial to comprehending the neurological consequences of the virus.…”

The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

“…Microglia, being a resident immune cell of the CNS, represents up to 20% of the glial population. Microglia are normally activated when the CNS is infected or injured and they move toward the site of infection (Qin et al, 2023). They are also responsible for destroying infected cells and releasing different types of cytotoxins that help in fighting invasive agents.…”

The complex role of the chemokine CX3CL1/Fractalkine in major depressive disorder: A narrative review of preclinical and clinical studies

“…Another important limitation is the fact that a single dose of LPS is mimetic of an acute inflammatory response within the murine CNS ( Yin et al, 2023 ) that may not be an effective representation of the chronic low-grade inflammation observed in MDD patients ( Berk et al, 2013a , Berk et al, 2013b ). Acute inflammation may result in compensatory anti-inflammatory microglial mechanisms ( Qin et al, 2023 ) in which FKN may act as a mediator. Hence, the roles of FKN in acute inflammatory responses in mice may vary from those observed in MDD patients – potentially explaining the discrepancies between LPS and CS murine models.…”