Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical...

Area of Science:

• Neuroscience
• Developmental Biology
• Immunology

Background:

• Neuroplasticity is crucial for brain development during childhood and adolescence.
• Neurodevelopmental disorders like autism are common, necessitating identification of plasticity disruptors.
• Inflammation is implicated as a potential disruptor of developmental plasticity.

Purpose of the Study:

• To identify common pathological processes disrupting neuroplasticity signatures.
• To investigate the role of inflammation in disrupting developmental cortical plasticity in vivo.
• To explore potential therapeutic targets for neurodevelopmental disorders.

Main Methods:

• A novel computational approach linked 436 transcriptional disease signatures with neuroplasticity signatures.
• The mouse ocular dominance model was used to assess experience-dependent plasticity in the primary visual cortex.
• Systemic lipopolysaccharide administration was used to induce inflammation in juvenile mice.

Main Results:

• Inflammation was identified as a common pathological process linked to disrupted plasticity signatures.
• Systemic inflammation suppressed cortical plasticity during the juvenile critical period.
• Inflammation induced specific transcriptional changes in molecular regulators within the primary visual cortex.

Conclusions:

• Inflammation poses unrecognized risks to postnatal brain development and plasticity.
• Targeting inflammation may be a viable strategy to mitigate the impact of neurodevelopmental disorders.
• Findings highlight the link between inflammation, neuroplasticity, and neurodevelopmental outcomes.