Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity

Abstract Given that thousands of chemicals released into the environment have the potential capacity to harm neurodevelopment, there is an urgent need to systematically evaluate their toxicity. Neurodevelopment is marked by critical periods of plasticity wherein neural circuits are refined by the en...

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Autores principales:	Milo R. Smith, Priscilla Yevoo, Masato Sadahiro, Christine Austin, Chitra Amarasiriwardena, Mahmoud Awawda, Manish Arora, Joel T. Dudley, Hirofumi Morishita
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Critical Period Integrated Bioinformatics Approach Significant Neurotoxicity Critical Pe Riod (CP) Ocular Dominance Index (ODI) Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f7c65e8dfa37436cb3d6888f13f93b7b
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spelling	oai:doaj.org-article:f7c65e8dfa37436cb3d6888f13f93b7b2021-12-02T15:08:11ZIntegrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity10.1038/s41598-018-34592-42045-2322https://doaj.org/article/f7c65e8dfa37436cb3d6888f13f93b7b2018-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34592-4https://doaj.org/toc/2045-2322Abstract Given that thousands of chemicals released into the environment have the potential capacity to harm neurodevelopment, there is an urgent need to systematically evaluate their toxicity. Neurodevelopment is marked by critical periods of plasticity wherein neural circuits are refined by the environment to optimize behavior and function. If chemicals perturb these critical periods, neurodevelopment can be permanently altered. Focusing on 214 human neurotoxicants, we applied an integrative bioinformatics approach using publically available data to identify dozens of neurotoxicant signatures that disrupt a transcriptional signature of a critical period for brain plasticity. This identified lead (Pb) as a critical period neurotoxicant and we confirmed in vivo that Pb partially suppresses critical period plasticity at a time point analogous to exposure associated with autism. This work demonstrates the utility of a novel informatics approach to systematically identify neurotoxicants that disrupt childhood neurodevelopment and can be extended to assess other environmental chemicals.Milo R. SmithPriscilla YevooMasato SadahiroChristine AustinChitra AmarasiriwardenaMahmoud AwawdaManish AroraJoel T. DudleyHirofumi MorishitaNature PortfolioarticleCritical PeriodIntegrated Bioinformatics ApproachSignificant NeurotoxicityCritical Pe Riod (CP)Ocular Dominance Index (ODI)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Critical Period Integrated Bioinformatics Approach Significant Neurotoxicity Critical Pe Riod (CP) Ocular Dominance Index (ODI) Medicine R Science Q
spellingShingle	Critical Period Integrated Bioinformatics Approach Significant Neurotoxicity Critical Pe Riod (CP) Ocular Dominance Index (ODI) Medicine R Science Q Milo R. Smith Priscilla Yevoo Masato Sadahiro Christine Austin Chitra Amarasiriwardena Mahmoud Awawda Manish Arora Joel T. Dudley Hirofumi Morishita Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity
description	Abstract Given that thousands of chemicals released into the environment have the potential capacity to harm neurodevelopment, there is an urgent need to systematically evaluate their toxicity. Neurodevelopment is marked by critical periods of plasticity wherein neural circuits are refined by the environment to optimize behavior and function. If chemicals perturb these critical periods, neurodevelopment can be permanently altered. Focusing on 214 human neurotoxicants, we applied an integrative bioinformatics approach using publically available data to identify dozens of neurotoxicant signatures that disrupt a transcriptional signature of a critical period for brain plasticity. This identified lead (Pb) as a critical period neurotoxicant and we confirmed in vivo that Pb partially suppresses critical period plasticity at a time point analogous to exposure associated with autism. This work demonstrates the utility of a novel informatics approach to systematically identify neurotoxicants that disrupt childhood neurodevelopment and can be extended to assess other environmental chemicals.
format	article
author	Milo R. Smith Priscilla Yevoo Masato Sadahiro Christine Austin Chitra Amarasiriwardena Mahmoud Awawda Manish Arora Joel T. Dudley Hirofumi Morishita
author_facet	Milo R. Smith Priscilla Yevoo Masato Sadahiro Christine Austin Chitra Amarasiriwardena Mahmoud Awawda Manish Arora Joel T. Dudley Hirofumi Morishita
author_sort	Milo R. Smith
title	Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity
title_short	Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity
title_full	Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity
title_fullStr	Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity
title_full_unstemmed	Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity
title_sort	integrative bioinformatics identifies postnatal lead (pb) exposure disrupts developmental cortical plasticity
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/f7c65e8dfa37436cb3d6888f13f93b7b
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Integrative bioinformatics identifies postnatal lead (Pb) exposure disrupts developmental cortical plasticity

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