Department of Biological Sciences, North Carolina State University, Raleigh, NC, 27695, USA.
Center for Human Health and the Environment, North Carolina State University, Raleigh, NC, 27695, USA.
Curr Environ Health Rep. 2018 Mar;5(1):145-157. doi: 10.1007/s40572-018-0185-0.
With the incidence of neurodevelopmental disorders on the rise, it is imperative to identify and understand the mechanisms by which environmental contaminants can impact the developing brain and heighten risk. Here, we report on recent findings regarding novel mechanisms of developmental neurotoxicity and highlight chemicals of concern, beyond traditionally defined neurotoxicants.
The perinatal window represents a critical and extremely vulnerable period of time during which chemical insult can alter the morphological and functional trajectory of the developing brain. Numerous chemical classes have been associated with alterations in neurodevelopment including metals, solvents, pesticides, and, more recently, endocrine-disrupting compounds. Although mechanisms of neurotoxicity have traditionally been identified as pathways leading to neuronal cell death, neuropathology, or severe neural injury, recent research highlights alternative mechanisms that result in more subtle but consequential changes in the brain and behavior. These emerging areas of interest include neuroendocrine and immune disruption, as well as indirect toxicity via actions on other organs such as the gut and placenta. Understanding of the myriad ways in which the developing brain is vulnerable to chemical exposures has grown tremendously over the past decade. Further progress and implementation in risk assessment is critical to reducing risk of neurodevelopmental disorders.
随着神经发育障碍的发病率不断上升,迫切需要确定和了解环境污染物影响发育中大脑并增加风险的机制。在这里,我们报告了关于发育神经毒性新机制的最新发现,并强调了除传统定义的神经毒物之外的关注化学物质。
围产期是一个关键且极其脆弱的时期,在此期间,化学物质的侵害可能会改变大脑发育的形态和功能轨迹。许多化学物质类别与神经发育的改变有关,包括金属、溶剂、农药,以及最近的内分泌干扰化合物。虽然神经毒性的机制传统上被确定为导致神经元细胞死亡、神经病理学或严重神经损伤的途径,但最近的研究强调了导致大脑和行为发生更微妙但更重要变化的替代机制。这些新出现的研究领域包括神经内分泌和免疫紊乱,以及通过对肠道和胎盘等其他器官的作用产生的间接毒性。在过去的十年中,人们对发育中大脑易受化学暴露影响的多种方式有了极大的了解。在风险评估方面取得进一步进展和实施对于降低神经发育障碍的风险至关重要。