title: Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration.
abstract: 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.
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, North Carolina 27599-7545, USA.|Carolina Institute for Developmental Disabilities, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599-7255, USA.
authors.forename: Brandon L
authors.initials: BL
authors.lastname: Pearson
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, North Carolina 27599-7545, USA.|Carolina Institute for Developmental Disabilities, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599-7255, USA.
authors.forename: Jeremy M
authors.identifier: http://orcid.org/0000-0003-3906-1663
authors.initials: JM
authors.lastname: Simon
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, North Carolina 27599-7545, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: McCoy
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, North Carolina 27599-7545, USA.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salazar
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, North Carolina 27599-7545, USA.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fragola
authors.affiliation: Department of Cell Biology and Physiology, UNC Neuroscience Center, University of North Carolina at Chapel Hill, 111 Mason Farm Road, Chapel Hill, North Carolina 27599-7545, USA.|Carolina Institute for Developmental Disabilities, University of North Carolina Chapel Hill, Chapel Hill, North Carolina 27599-7255, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zylka
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001321:Autistic Disorder / Q000235:genetics* / Q000517:prevention & control; D001921:Brain / Q000187:drug effects*; D002478:Cells, Cultured; D004781:Environmental Exposure; D005659:Fungicides, Industrial / Q000737:chemistry / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000517:prevention & control; D010575:Pesticides / Q000737:chemistry / Q000633:toxicity; D018570:Risk Assessment; D012307:Risk Factors; D012402:Rotenone / Q000737:chemistry / Q000633:toxicity; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D005659:Fungicides, Industrial; D010575:Pesticides; D012402:Rotenone