Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration
Citations Over TimeTop 10% of 2016 papers
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.
Related Papers
- → Correct Assay of Complex I Activity in Human Skin Fibroblasts by Timely Addition of Rotenone(2008)13 cited
- → Novel reactions of rotenone(1976)7 cited
- 미토콘드리아 전자전달계의 인위적 차단과 유산소 훈련이 항산화 체계 및 에너지 대사에 미치는 영향(2002)
- 장기간의 유산소 훈련과 Rotenone 투여가 Glycogen 및 효소 활성변화에 미치는 영향(2003)
- → Author Index for Volume 239(1997)