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

pyraclostrobin trifloxystrobin famoxadone fenamidone autism brain aging neurodegeneration

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#1 Logic

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Posted 03 April 2016 - 09:53 PM


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-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.

 

Usage of complex I inhibitors (rotenone and pyridaben) is low and unchanging, with the notable exception of fenpyroximate, the most potent superoxide producer we identified (concentration for half-maximum response (EC50)=0.007 μM; Supplementary Fig. 8b). Many cluster 2 residues were found on conventionally raised food commodities, particularly leafy green vegetables, and were detected at relatively high levels, up to 20 p.p.m. in the case of pyraclostrobin. These data suggest significant human exposure potential to many of the chemicals in cluster 2.

 

http://www.nature.co...comms11173.html


Edited by Logic, 03 April 2016 - 09:57 PM.






Also tagged with one or more of these keywords: pyraclostrobin, trifloxystrobin, famoxadone, fenamidone, autism, brain aging, neurodegeneration

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