The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

Abstract

: The bidirectional communication between neurons and microglia is fundamental for the proper functioning of the central nervous system (CNS). Chemokines and clusters of differentiation (CD) along with their receptors represent ligand-receptor signalling that is uniquely important for neuron – microglia communication. Among these molecules, CX3CL1 (fractalkine) and CD200 (OX-2 membrane glycoprotein) come to the fore because of their cell-type-specific localization. They are principally expressed by neurons when their receptors, CX3CR1 and CD200R, respectively, are predominantly present on the microglia, resulting in the specific axis which maintains the CNS homeostasis. Disruptions to this balance are suggested as contributors or even the basis for many neurological diseases. : In this review, we discuss the roles of CX3CL1, CD200 and their receptors in both physiological and pathological processes within the CNS. We want to underline the critical involvement of these molecules in controlling neuron – microglia communication, noting that dysfunctions in their interactions constitute a key factor in severe neurological diseases, such as schizophrenia, depression and neurodegeneration-based conditions.

The prenatal challenge with lipopolysaccharide and polyinosinic:polycytidylic acid disrupts CX3CL1-CX3CR1 and CD200-CD200R signalling in the brains of male rat offspring: a link to schizophrenia-like behaviours

“…There is a growing body of evidence that in the CNS, preservation of proper neuron-microglia interactions is crucial for brain development and homeostasis [ 1 , 2 , 54 ]. This dynamic crosstalk is under the control of endogenous factors, including the CX3CL1-CX3CR1 and CD200-CD200R axes.…”

“…Bidirectional communication between neurons and microglia is fundamental for the homeostasis and biological function of the central nervous system (CNS). This crosstalk orchestrates the balance for proper neurodevelopmental processes, including neurogenesis, synaptogenesis, synaptic pruning, axonal growth, astrocyte maturation, mitochondrial biogenesis, myelination and blood-brain barrier integrity [ 1 , 2 ]. This communication is also crucial for the control of the immune response [ 3 – 5 ].…”

Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems

“…Microglia activity is regulated by various mechanisms within the central nervous system (CNS), including the exchange of signals linking microglia with other brain cells, particularly neurons [ 25 ]. This communication determines normal neurodevelopmental processes and blood–brain barrier integrity [ 26 , 27 ]. Malfunctions of this interaction upregulate the phagocytic activity, mobility, and release of pro-inflammatory factors by microglia [ 10 ].…”

Epigenetics and Communication Mechanisms in Microglia Activation with a View on Technological Approaches

“…Indeed, the dynamic interactions between microglia and neurons influence the maintenance of homeostasis and the proper neuronal functioning of the healthy brain. More specifically, neuron–microglia communication is involved in neuronal development, synaptic plasticity, regulation of angiogenesis and programmed cell death besides immune response [ 8 ]. In pathological states, the bidirectional dialogue perturbation promotes microglia activation and the consequent increased inflammatory processes which in turn contribute to altering synaptic functions, plasticity and cognitive deficits, responsible for multiple brain pathologies, such as multiple sclerosis (MS), Alzheimer’s disease (AD) and Parkinson’s disease (PD).…”