Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
| Autor: | Eric S. McCoy, Gabriela Salazar, Mark J. Zylka, Jeremy M. Simon, Giulia Fragola, Brandon L. Pearson |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Science General Physics and Astronomy Disease Biology Bioinformatics Microtubules Risk Assessment Article Antioxidants General Biochemistry Genetics and Molecular Biology Transcriptome Mice 03 medical and health sciences chemistry.chemical_compound Risk Factors Rotenone medicine Animals Autistic Disorder Pesticides Cells Cultured Regulation of gene expression Genetics Multidisciplinary Neurodegeneration Brain Neurodegenerative Diseases Environmental Exposure General Chemistry Environmental exposure medicine.disease Fungicides Industrial 3. Good health 030104 developmental biology Gene Expression Regulation chemistry Autism Sulforaphane |
| Zdroj: | Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-12 (2016) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/ncomms11173 |
| Popis: | 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. This study presents gene expression responses of cultured brain cells to hundreds of chemicals found in the environment and in food. The authors identified chemicals that induce transcriptomic profiles that overlap those seen in human brains affected with autism, aging, and neurodegeneration. |
| Databáze: | OpenAIRE |
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