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

Pearson, Brandon L.; Simon, Jeremy M.; McCoy, Eric S.; Salazar, Gabriela; Fragola, Giulia; Zylka, Mark J.

doi:10.1038/ncomms11173

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

Published Date:

Mar 31 2016

Publisher's site:

http://dx.doi.org/10.1038/ncomms11173 New Site Icon

Source:

Nat Commun. 2016; 7.

[PDF - 1.26 MB]

Details:

Personal Authors:

Pearson, Brandon L. ; Simon, Jeremy M. ; McCoy, Eric S. ; Salazar, Gabriela ; Fragola, Giulia ; ... More ▼

Keywords:

[+]

Pubmed ID:

27029645

Pubmed Central ID:

PMC4821887

Description:

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.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

5T32HD040127/HD/NICHD NIH HHS/United States
DP1 ES024088/ES/NIEHS NIH HHS/United States
DP1ES024088/DP/NCCDPHP CDC HHS/United States
P30 HD003110/HD/NICHD NIH HHS/United States
P30 NS045892/NS/NINDS NIH HHS/United States
P30HD03110/HD/NICHD NIH HHS/United States
P30NS045892/NS/NINDS NIH HHS/United States
U54 HD079124/HD/NICHD NIH HHS/United States

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