Allen Joshua L, Liu Xiufang, Pelkowski Sean, Palmer Brian, Conrad Katherine, Oberdörster Günter, Weston Douglas, Mayer-Pröschel Margot, Cory-Slechta Deborah A
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, New York, USA.
Environ Health Perspect. 2014 Sep;122(9):939-45. doi: 10.1289/ehp.1307984. Epub 2014 Jun 5.
Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression.
We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development.
We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified.
We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males.
We observed brain region- and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans.
空气污染已被证明与儿童和成人的不良神经及行为健康影响相关。近期研究将空气污染物暴露与不良神经发育结果联系起来，包括自闭症、认知衰退、缺血性中风、精神分裂症和抑郁症风险增加。
我们试图研究暴露于超细浓缩环境颗粒物（CAPs）对中枢神经系统（CNS）发育产生不利影响的机制。
我们使用哈佛大学浓缩环境颗粒物系统，在出生后第4 - 7天和第10 - 13天将C57BL6/J小鼠暴露于超细（< 100 nm）CAPs或过滤空气中，在暴露停止后24小时或40天对动物实施安乐死。另一组雄性小鼠在出生后第270天暴露，对侧脑室面积、胶质细胞激活、CNS细胞因子以及单胺和氨基酸神经递质进行定量分析。
我们观察到，暴露于CAPs的雄性小鼠优先出现脑室扩大（即侧脑室扩张），且这种情况持续到成年早期。此外，暴露于CAPs的雄性小鼠通常表现出对神经发育重要的CNS细胞因子减少，而在暴露于CAPs的雌性小鼠中，我们观察到CNS细胞因子增加所表明的神经炎症反应。我们还发现，多个脑区的CNS神经递质和胶质细胞激活存在性别依赖性变化，且暴露于CAPs的雄性小鼠海马谷氨酸增加。
我们观察到，暴露于CAPs的雄性和雌性小鼠在细胞因子和神经递质方面存在脑区和性别依赖性改变。仅在暴露于CAPs的雄性小鼠中观察到侧脑室扩张（即脑室扩大）。脑室扩大是一种神经病理学特征，与不良神经发育结果、自闭症和精神分裂症相关。我们的研究结果表明，对神经发育重要的神经化学物质的改变和侧脑室扩张可能在机制上与人类环境空气污染物暴露和不良神经/神经发育结果之间的关联有关。
