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 is examined.
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.
It is proposed that microglia occupy a central position at the interface of these processes because of their dual roles in circuit remodeling and immune surveillance and highlights disease-modifying therapeutic strategies aimed at restoring microglial homeostasis to potentially mitigate the self-sustaining pathology in...
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Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with wide differences in cognitive, behavioral, and adaptive outcomes across the lifespan. Current evidence suggests that part of this heterogeneity may be related to interactions among genetic susceptibility, environmental exposures, and im...
R. Viterbo, Rosalba Tritto, Dario Sardella et al.· International Journal of Mol...· 0 citations
This review examines ASD from the perspective of lifelong neuronal vulnerability, highlighting how genetically diverse ASD-associated genes converge on common biological mechanisms that remain active beyond development.
A. Palacios-Muñoz· International Journal of Mol...· 0 citations
Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous neurodevelopmental condition arising from diverse genetic, epigenetic, and environmental influences. Increasing evidence suggests that immune dysregulation and sustained neuroinflammatory mechanisms contribute to the pathophysiology of a biol...
R. I. Gabr· Developmental Neurobiology· 0 citations
It is shown that 24S,25-epoxycholesterol, an oxysterol enriched in the fetal brain and dysregulated in NDDs, enhances neurogenesis while altering the distribution of GABAergic neuronal subtypes, suggesting that aberrant oxysterol signaling contributes to the pathogenesis of NDDs.
Maria Cruz-Santos, E. Kidd, Zongze Li et al.· Translational Psychiatry· 0 citations
Background Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication differences and restricted, repetitive behaviors. Convergent evidence implicates prefrontal cortex (PFC) circuit dysregulation and chronic neuroimmune activation in ASD. Despite increasing off-label use of...