title: Integrative Analysis of Disease Signatures Shows Inflammation Disrupts Juvenile Experience-Dependent Cortical Plasticity.
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 plasticityin vivousing 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.
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Milo R
authors.initials: MR
authors.lastname: Smith
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Poromendro
authors.initials: P
authors.lastname: Burman
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Masato
authors.identifier: 0000-0003-4164-565X
authors.initials: M
authors.lastname: Sadahiro
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Brian A
authors.identifier: 0000-0003-2110-1145
authors.initials: BA
authors.lastname: Kidd
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Dudley
authors.affiliation: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
authors.forename: Hirofumi
authors.identifier: 0000-0002-1045-1337
authors.initials: H
authors.lastname: Morishita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000465:Algorithms; D000818:Animals; D002540:Cerebral Cortex / Q000254:growth & development* / Q000276:immunology*; D003423:Critical Period, Psychological; D023882:Dominance, Ocular / Q000502:physiology; D004926:Escherichia coli; D007249:Inflammation / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046228:Microarray Analysis; D008839:Microelectrodes; D009473:Neuronal Plasticity / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012683:Sensory Deprivation / Q000502:physiology; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; C120222:Lynx1 protein, mouse; D008562:Membrane Glycoproteins; D009479:Neuropeptides
keywords: bioinformatics; critical period; inflammation; plasticity; transcriptome; visual cortex 