Cited by 127Pesticide Exposure and ToxicityHealth, Environment, Cognitive AgingAlzheimer's disease research and treatments

Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration

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Pearson, Brandon L., Simon, Jeremy M., McCoy, Eric S., Salazar, Gabriela, Fragola, Giulia, Zylka, Mark J.·2016·Nature Communications

Abstract

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)
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
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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