Neurobiology of microglial action in CNS injuries: Receptor-mediated signaling mechanisms and functional roles

Abstract

Microglia are the first line of immune defense against central nervous system (CNS) injuries and disorders. These highly plastic cells play dualistic roles in neuronal injury and recovery and are known for their ability to assume diverse phenotypes. A broad range of surface receptors are expressed on microglia and mediate microglial ‘On’ or ‘Off’ responses to signals from other host cells as well as invading microorganisms. The integrated actions of these receptors result in tightly regulated biological functions, including cell mobility, phagocytosis, the induction of acquired immunity, and trophic factor/inflammatory mediator release. Over the last few years, significant advances have been made towards deciphering the signaling mechanisms related to these receptors and their specific cellular functions. In this review, we describe the current state of knowledge of the surface receptors involved in microglial activation, with an emphasis on their engagement of distinct functional programs and their roles in CNS injuries. It will become evident from this review that microglial homeostasis is carefully maintained by multiple counterbalanced strategies, including, but not limited to, ‘On’ and ‘Off’ receptor signaling. Specific regulation of theses microglial receptors may be a promising therapeutic strategy against CNS injuries.

Adverse childhood experiences influence the detrimental effect of bipolar disorder and schizophrenia on cortico-limbic grey matter volumes

“…Neuroinflammation has been reported in patients with psychiatric disorders (Najjar et al, 2013), and is typically associated with microglial activation. A chronic activation of the immune system by microglia would produce cytokines that will render the brain vulnerable and unstable thus leading to mood disturbances (Schroeter et al, 2011) and to behavioural and cognitive deficits (Barichello et al, 2013;Hu et al, 2014). Indeed, increased markers of excitotoxicity and neuroinflammation have been reported in postmortem frontal cortex of both BD (Rao et al, 2010) and SCZ patients (Bayer et al, 1999;Radewicz et al, 2000).…”

SIRP/CD47 signaling in neurological disorders

“…Due to their janus-like roles, microglia are well-regulated by a variety of mechanisms so that they can be promptly switched on as the first responders to noxious stimuli and rapidly turned off to avoid unwanted effects. Many surface recognition receptors on microglia have been identified to sense the “turning on” or “turning off” signals released from other CNS cells and play critical role in modulating microglial responses in many CNS injuries and neurodegerative diseases (Hu et al, 2014b). …”

An Update on Inflammation in the Acute Phase of Intracerebral Hemorrhage

“…Besides, inflammation and immune cells are crucial to the repair and regeneration of brain tissue during the late stage [46][47][48]. Longterm suppression of inflammation may affect brain tissue repair in the late stage of ICH, and this is worrisome.…”