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

eNeuro. 2017 Jan 18;3(6):ENEURO.0240-16.2016. doi: 10.1523/ENEURO.0240-16.2016. eCollection Nov-Dec 2016.

Abstract

Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders.

Keywords: bioinformatics; critical period; inflammation; plasticity; transcriptome; visual cortex.

MeSH terms

  • Algorithms
  • Animals
  • Cerebral Cortex / growth & development*
  • Cerebral Cortex / immunology*
  • Critical Period, Psychological
  • Dominance, Ocular / physiology
  • Escherichia coli
  • Inflammation / metabolism*
  • Lipopolysaccharides
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microarray Analysis
  • Microelectrodes
  • Neuronal Plasticity / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism
  • Polymerase Chain Reaction
  • Sensory Deprivation / physiology
  • Transcription, Genetic
  • Transcriptome

Substances

  • Lipopolysaccharides
  • Lynx1 protein, mouse
  • Membrane Glycoproteins
  • Neuropeptides