TY - JOUR
T1 - Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen
AU - Smith, Milo R.
AU - Yevoo, Priscilla
AU - Sadahiro, Masato
AU - Readhead, Ben
AU - Kidd, Brian
AU - Dudley, Joel T.
AU - Morishita, Hirofumi
N1 - Publisher Copyright:
© 2020 Milo R. Smith et al.
PY - 2020
Y1 - 2020
N2 - The tens of thousands of industrial and synthetic chemicals released into the environment have an unknown but potentially significant capacity to interfere with neurodevelopment. Consequently, there is an urgent need for systematic approaches that can identify disruptive chemicals. Little is known about the impact of environmental chemicals on critical periods of developmental neuroplasticity, in large part, due to the challenge of screening thousands of chemicals. Using an integrative bioinformatics approach, we systematically scanned 2001 environmental chemicals and identified 50 chemicals that consistently dysregulate two transcriptional signatures of critical period plasticity. These chemicals included pesticides (e.g., pyridaben), antimicrobials (e.g., bacitracin), metals (e.g., mercury), anesthetics (e.g., halothane), and other chemicals and mixtures (e.g., vehicle emissions). Application of a chemogenomic enrichment analysis and hierarchical clustering across these diverse chemicals identified two clusters of chemicals with one that mimicked an immune response to pathogen, implicating inflammatory pathways and microglia as a common chemically induced neuropathological process. Thus, we established an integrative bioinformatics approach to systematically scan thousands of environmental chemicals for their ability to dysregulate molecular signatures relevant to critical periods of development.
AB - The tens of thousands of industrial and synthetic chemicals released into the environment have an unknown but potentially significant capacity to interfere with neurodevelopment. Consequently, there is an urgent need for systematic approaches that can identify disruptive chemicals. Little is known about the impact of environmental chemicals on critical periods of developmental neuroplasticity, in large part, due to the challenge of screening thousands of chemicals. Using an integrative bioinformatics approach, we systematically scanned 2001 environmental chemicals and identified 50 chemicals that consistently dysregulate two transcriptional signatures of critical period plasticity. These chemicals included pesticides (e.g., pyridaben), antimicrobials (e.g., bacitracin), metals (e.g., mercury), anesthetics (e.g., halothane), and other chemicals and mixtures (e.g., vehicle emissions). Application of a chemogenomic enrichment analysis and hierarchical clustering across these diverse chemicals identified two clusters of chemicals with one that mimicked an immune response to pathogen, implicating inflammatory pathways and microglia as a common chemically induced neuropathological process. Thus, we established an integrative bioinformatics approach to systematically scan thousands of environmental chemicals for their ability to dysregulate molecular signatures relevant to critical periods of development.
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U2 - 10.1155/2020/1673897
DO - 10.1155/2020/1673897
M3 - Article
C2 - 32454811
AN - SCOPUS:85085305917
VL - 2020
JO - Neural Plasticity
JF - Neural Plasticity
SN - 2090-5904
M1 - 1673897
ER -