Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-34592-4
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Funding
- National Institute of Child Health and Human Development -Interdisciplinary Training in Systems and Developmental Biology and Birth Defects [T32H-D0-75735]
- Mindich Child Health and Development Institute Pilot Fund
- Knights Templar Eye Foundation
- March of Dimes
- Whitehall Foundation
- Harris Family Foundation
- National Institutes of Health [P30-ES-023515, R01-DK-098242, U54-CA189201, R56-AG058469, R01-EY-024918, R01-EY-026053, R21 MH106919]
- EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [T32HD075735] Funding Source: NIH RePORTER
- NATIONAL CANCER INSTITUTE [U54CA189201] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR001433] Funding Source: NIH RePORTER
- NATIONAL EYE INSTITUTE [R21EY026702, R01EY024918, R01EY026053] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK098242] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES023515] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R21MH106919] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS105119] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R56AG058469] Funding Source: NIH RePORTER
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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.
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