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

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  • Brandon L. Pearson

    (UNC Neuroscience Center, University of North Carolina at Chapel Hill
    Carolina Institute for Developmental Disabilities, University of North Carolina Chapel Hill)

  • Jeremy M. Simon

    (UNC Neuroscience Center, University of North Carolina at Chapel Hill
    Carolina Institute for Developmental Disabilities, University of North Carolina Chapel Hill)

  • Eric S. McCoy

    (UNC Neuroscience Center, University of North Carolina at Chapel Hill)

  • Gabriela Salazar

    (UNC Neuroscience Center, University of North Carolina at Chapel Hill)

  • Giulia Fragola

    (UNC Neuroscience Center, University of North Carolina at Chapel Hill)

  • Mark J. Zylka

    (UNC Neuroscience Center, University of North Carolina at Chapel Hill
    Carolina Institute for Developmental Disabilities, University of North Carolina Chapel Hill)

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.

Suggested Citation

  • Brandon L. Pearson & Jeremy M. Simon & Eric S. McCoy & Gabriela Salazar & Giulia Fragola & Mark J. Zylka, 2016. "Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration," Nature Communications, Nature, vol. 7(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11173
    DOI: 10.1038/ncomms11173
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    Cited by:

    1. Biggi, Gianluca & Giuliani, Elisa & Martinelli, Arianna & Benfenati, Emilio, 2022. "Patent Toxicity," Research Policy, Elsevier, vol. 51(1).
      • Gianluca Biggi & Elisa Giuliani & Arianna Martinelli, 2020. "Patent Toxicity," LEM Papers Series 2020/33, Laboratory of Economics and Management (LEM), Sant'Anna School of Advanced Studies, Pisa, Italy.

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