Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
Open accessAbstract
Environmental factors, including pesticides, have been linked to autism and neurodegeneration risk using retrospective epidemiological studies. Here we sought to prospectively identify chemicals that share transcriptomic signatures with neurological disorders, by exposing mouse cortical neuron-enriched cultures to hundreds of chemicals commonly found in the environment and on food. We find that rotenone, a pesticide associated with Parkinson’s disease risk, and certain fungicides, including pyraclostrobin, trifloxystrobin, famoxadone and fenamidone, produce transcriptional changes in vitro that are similar to those seen in brain samples from humans with autism, advanced age and neurodegeneration (Alzheimer’s disease and Huntington’s disease). These chemicals stimulate free radical production and disrupt microtubules in neurons, effects that can be reduced by pretreating with a microtubule stabilizer, an antioxidant, or with sulforaphane. Our study provides an approach to prospectively identify environmental chemicals that transcriptionally mimic autism and other brain disorders.
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Transcriptional alterations in response to chemical exposures that mimic changes seen in brain samples from autism patients have also been reported recently.
“Transcriptional alterations in response to chemical exposures that mimic changes seen in brain samples from autism patients have also been reported recently34.”
From Fetal and postnatal metal dysregulation in autism (2017) · cites this paper as [34]
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- Authors
- Pearson, B. L., Simon, J. M., McCoy, E. S., Salazar, G., Fragola, G., & Zylka, M. J.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Zylka, Mark J.
- Venue
- Nature Communications
- Published
- 2016-03-31
- Volume
- 7
- Issue
- 1
- Pages
- 11173-11173
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4821887
- OpenAlex
- W2318680930
- Cited by
- 127
- References
- 66
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 9 · 2023: 9 · 2022: 20 · 2021: 13 · 2020: 14 · 2019: 18 · 2018: 11 · 2017: 12 · 2016: 8
- FWCI
- 19.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- UNC Libraries
- Funders
- National Institute of Neurological Disorders and Stroke (P30NS045892)
- National Institute of Environmental Health Sciences (DP1ES024088, P30ES010126)
- National Center for Chronic Disease Prevention and Health Promotion (DP1ES024088)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD079124, P30HD003110, T32HD040127)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- autism spectrum disorder, brain aging, neurodegeneration, environmental chemicals, pesticide exposure, fungicides, rotenone, pyraclostrobin, trifloxystrobin, famoxadone, fenamidone, gene expression signatures, free radical generation, microtubule disruption, sulforaphane, Parkinson's disease, Alzheimer's disease, Huntington's disease, neurotoxicity
- MeSH terms
- Animals, Antioxidants, Autistic Disorder, Brain, Cells, Cultured, Environmental Exposure, Fungicides, Industrial, Gene Expression Regulation, Microtubules, Pesticides, Risk Factors, Rotenone, Transcription, Genetic, Risk Assessment, Neurodegenerative Diseases, Mice
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