Role of Epigenetically Active Environmental Compounds in Neurodevelopmental Disorders

项目摘要 神经发育障碍（NDD）越来越多地被认为起源于神经发育障碍的调节异常。 早期的大脑发育，这代表了对环境化合物的脆弱性。 环境化合物可以通过表观遗传机制改变神经发育，这可能不会诱导 大规模的细胞死亡，但通过其对干细胞命运和谱系的表观遗传效应改变脑功能 发展然而，系统地研究环境对表观遗传影响的工具， 神经系统缺乏。在这里，我们采用表观遗传景观显微成像（MIEL）， 筛选ToxCast III期化学文库（4700种化合物），并表征改变表观遗传的命中物 人类神经前体的景观而不诱导细胞毒性。认识到环境损害， 了解其作用机制将有助于制定旨在 避免这种损害，并在暴露不可避免时开发解毒剂和保护剂。

PROJECT SUMMARY Neurodevelopmental disorders (NDDs), are increasingly recognized as originating from dysregulation of early brain development, which represents a window of vulnerability to environmental compounds. Environmental compounds may alter neurodevelopment via epigenetic mechanisms, which may not induce massive cell death, but change the brain function through their epigenetic effect on stem cell fate and lineage development. However, tools to systematically examine the epigenetic impact of environment on neurodevelopment are lacking. Here we employ Microscopic Imaging of Epigenetic Landscape (MIEL) to screen ToxCast Phase III chemical library (4700 compounds) and to characterize hits that alter epigenetic landscape of human neural precursors without inducing cytotoxicity. Recognizing environmental insults and understanding their mechanism of action will enable the development of regulations and guidelines aimed at avoiding such insults and the development of antidotes and protective agents when exposure is unavoidable.