Neuroimmune Dysregulation and Synaptic Pruning in Autism Spectrum Disorder

Abstract

Simple Summary Autism spectrum disorder (ASD) affects millions of children and adults worldwide, yet its underlying causes remain incompletely understood. This review examines a growing body of evidence suggesting that the brain’s immune system—long thought to be isolated from the rest of the body—plays a critical role in shaping how neural connections are formed and refined during development. During early life, the brain produces an excess of connections between nerve cells, and those that are not strengthened through experience are normally eliminated through a process called “synaptic pruning.” This pruning process is orchestrated by immune molecules and specialized brain-resident immune cells called microglia. In ASD, this pruning mechanism appears to be disrupted, leading to either too many or improperly organized connections that may contribute to the characteristic features of the condition, including difficulties with social communication and sensory processing. The review also explores how inflammation elsewhere in the body can influence brain immune function. Understanding these mechanisms opens new possibilities for developing treatments that target the underlying biological processes rather than just managing symptoms.