Neuroinflammation in preterm babies and autism spectrum disorders

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Autism spectrum disorder (ASD) is influenced by genetic anomalies, with each factor contributing minimally.
• Environmental factors, particularly preterm birth, significantly elevate ASD risk (10-fold increase).
• Preterm birth is frequently linked to maternal/fetal inflammation, potentially causing neonatal inflammatory syndrome.

Purpose of the Study:

• To explore the hypothesis that perinatal inflammation in preterm infants, combined with a genetic risk background, deregulates brain development, leading to ASD.
• To investigate the role of inflammation in altering brain connectivity and synaptogenesis in preterm infants who develop ASD.

Main Methods:

• The study integrates existing experimental evidence linking fetal inflammation to ASD-like behavioral symptoms.
• It examines the impact of inflammation on microglia function, essential for synaptogenesis.
• Compares the phenotype of preterm infants with ASD to term-born peers.

Main Results:

• Experimental links demonstrate that fetal inflammation can lead to ASD-consistent behavioral symptoms.
• Preterm infants exhibit connectivity deficits; most ASD-associated genes encode synaptic proteins, indicating connectivity pathologies.
• Perinatal inflammation diverts microglia from homeostatic roles to inflammatory phenotypes, impairing synaptogenesis.

Conclusions:

• Inflammation during the perinatal period in preterm infants, especially with a genetic predisposition, is hypothesized to disrupt normal brain development.
• This disruption affects brain connectivity and synaptogenesis, potentially underlying the development of ASD in this population.
• Preterm infants with ASD present a distinct phenotype, suggesting unique developmental trajectories influenced by early inflammatory insults.