TY - JOUR
T1 - Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
AU - Pearson, Brandon L.
AU - Simon, Jeremy M.
AU - McCoy, Eric S.
AU - Salazar, Gabriela
AU - Fragola, Giulia
AU - Zylka, Mark J.
PY - 2016/3/31
Y1 - 2016/3/31
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84962909861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962909861&partnerID=8YFLogxK
U2 - 10.1038/ncomms11173
DO - 10.1038/ncomms11173
M3 - Article
AN - SCOPUS:84962909861
VL - 7
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 11173
ER -