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

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-enric...

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Main Authors:	Pearson, Brandon L., Simon, Jeremy M., McCoy, Eric S., Salazar, Gabriela, Fragola, Giulia, Zylka, Mark J.
Format:	Online
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821887/

id	pubmed-4821887
recordtype	oai_dc
spelling	pubmed-48218872016-04-17 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. Article 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. Nature Publishing Group 2016-03-31 /pmc/articles/PMC4821887/ /pubmed/27029645 http://dx.doi.org/10.1038/ncomms11173 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Pearson, Brandon L. Simon, Jeremy M. McCoy, Eric S. Salazar, Gabriela Fragola, Giulia Zylka, Mark J.
spellingShingle	Pearson, Brandon L. Simon, Jeremy M. McCoy, Eric S. Salazar, Gabriela Fragola, Giulia Zylka, Mark J. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
author_facet	Pearson, Brandon L. Simon, Jeremy M. McCoy, Eric S. Salazar, Gabriela Fragola, Giulia Zylka, Mark J.
author_sort	Pearson, Brandon L.
title	Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
title_short	Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
title_full	Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
title_fullStr	Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
title_full_unstemmed	Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
title_sort	identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
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.
publisher	Nature Publishing Group
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821887/
_version_	1613562664465727488

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

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