Microglia along sex lines: From brain colonization, maturation and function, to implication in neurodevelopmental disorders

Abstract

In addition to their traditional role as immune sentinels, recent discoveries over the last decade have shown that microglial functions now include regulation of neuronal/glial cell migration, differentiation and maturation, as well as neuronal network formation. It was thus proposed that disruption of these microglial roles, during critical periods of brain development, could lead to the pathological onset of several neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, schizophrenia, and major depressive disorder. The prevalence of these disorders exhibits a clear distinction along sex lines with very little known about the mechanisms underlying this difference. One of the fundamental discoveries that arose from recent research into the physiological roles of microglia in neurodevelopment is their sexual dimorphism, raising the intriguing possibility that sex differences in microglial colonization, maturation and/or function in the developing brain could underlie the emergence of various neurodevelopmental disorders. This review discusses the physiological roles of microglia across neurodevelopment, these roles in the two sexes, and the recent evidence that microglial sexually dimorphic nature may contribute, at least partially, to neurodevelopmental disorders.

Keywords: Animal models; Human; Microglia; Neurodevelopment; Neurodevelopmental disorders; Sexual dimorphism.