Microglial regulation of white matter development and its disruption in autism spectrum disorder

Abstract

White matter, comprising approximately 50% of the human brain, is crucial for efficient neuronal signaling and a wide range of brain functions, including social cognition, sensation, memory, motor control, and information integration across cortical brain regions in the service of perception and cognition. White matter, composed of myelinated axons, results from complex interactions between different cell types, with oligodendrocytes (OLs) and microglia playing integral roles. Microglia, the brain's resident immune cells, regulate oligodendrogenesis through phagocytosis and molecular signaling, for example through cytokines, which promote and inhibit maturation stages of OL lineage cells. Maternal immune activation (MIA) is a recognized risk factor for neurodevelopmental disorders, especially autism spectrum disorder (ASD). The physiological presentation of ASD includes white matter abnormalities and immune dysregulation. Emerging evidence indicates that MIA may reduce microglial reactivity and alter cytokine release in offspring, potentially disrupting the delicate balance required for proper white matter development. Understanding the intricate interplay between oligodendrocytes, microglia, inflammation, and white matter development in the context of MIA provides valuable insights into the etiology of and core symptoms of ASD and possible therapeutic targets.