Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen
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 a...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2020/1673897 |
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| author | Milo R. Smith Priscilla Yevoo Masato Sadahiro Ben Readhead Brian Kidd Joel T. Dudley Hirofumi Morishita |
| author_facet | Milo R. Smith Priscilla Yevoo Masato Sadahiro Ben Readhead Brian Kidd Joel T. Dudley Hirofumi Morishita |
| author_sort | Milo R. Smith |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ef35611faa849c8a895af905479af3d |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-5ef35611faa849c8a895af905479af3d2025-02-03T00:58:46ZengWileyNeural Plasticity2090-59041687-54432020-01-01202010.1155/2020/16738971673897Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to PathogenMilo R. Smith0Priscilla Yevoo1Masato Sadahiro2Ben Readhead3Brian Kidd4Joel T. Dudley5Hirofumi Morishita6Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USAInstitute for Next Generation Healthcare, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USADepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York NY 10029, USAThe 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.http://dx.doi.org/10.1155/2020/1673897 |
| spellingShingle | Milo R. Smith Priscilla Yevoo Masato Sadahiro Ben Readhead Brian Kidd Joel T. Dudley Hirofumi Morishita Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen Neural Plasticity |
| title | Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen |
| title_full | Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen |
| title_fullStr | Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen |
| title_full_unstemmed | Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen |
| title_short | Systematic Analysis of Environmental Chemicals That Dysregulate Critical Period Plasticity-Related Gene Expression Reveals Common Pathways That Mimic Immune Response to Pathogen |
| title_sort | systematic analysis of environmental chemicals that dysregulate critical period plasticity related gene expression reveals common pathways that mimic immune response to pathogen |
| url | http://dx.doi.org/10.1155/2020/1673897 |
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