Department of Psychology and Neuroscience, Duke University, Durham, North Carolina 27710, USA.
Environ Health Perspect. 2013 Sep;121(9):1075-82. doi: 10.1289/ehp.1306560. Epub 2013 Jul 3.
Low socioeconomic status is consistently associated with reduced physical and mental health, but the mechanisms remain unclear. Increased levels of urban air pollutants interacting with parental stress have been proposed to explain health disparities in respiratory disease, but the impact of such interactions on mental health is unknown.
We aimed to determine whether prenatal air pollution exposure and stress during pregnancy act synergistically on offspring to induce a neuroinflammatory response and subsequent neurocognitive disorders in adulthood.
Mouse dams were intermittently exposed via oropharyngeal aspiration to diesel exhaust particles (DEP; 50 μg × 6 doses) or vehicle throughout gestation. This exposure was combined with standard housing or nest material restriction (NR; a novel model of maternal stress) during the last third of gestation.
Adult (postnatal day 60) offspring of dams that experienced both stressors (DEP and NR) displayed increased anxiety, but only male offspring of this group had impaired cognition. Furthermore, maternal DEP exposure increased proinflammatory interleukin (IL)-1β levels within the brains of adult males but not females, and maternal DEP and NR both decreased anti-inflammatory IL-10 in male, but not female, brains. Similarly, only DEP/NR males showed increased expression of the innate immune recognition gene toll-like receptor 4 (Tlr4) and its downstream effector, caspase-1.
These results show that maternal stress during late gestation increases the susceptibility of offspring-particularly males-to the deleterious effects of prenatal air pollutant exposure, which may be due to a synergism of these factors acting on innate immune recognition genes and downstream neuroinflammatory cascades within the developing brain.
低社会经济地位与身心健康状况下降密切相关，但具体机制尚不清楚。有研究提出，城市空气污染物水平升高与父母压力相互作用，可能导致呼吸道疾病方面的健康差异，但这种相互作用对心理健康的影响尚不清楚。
我们旨在确定孕期空气污染暴露和孕期压力是否会协同作用于后代，导致成年后出现神经炎症反应和随后的神经认知障碍。
通过口咽吸入方式，使孕鼠间歇性暴露于柴油机排气颗粒物（DEP；50μg×6 剂）或载体中，贯穿整个妊娠期。在妊娠后期的最后三分之一时间里，这种暴露与标准住房或巢材限制（NR；一种新的母体应激模型）相结合。
经历了双重应激源（DEP 和 NR）的孕鼠的成年（出生后第 60 天）后代表现出焦虑增加，但只有这一组的雄性后代出现认知障碍。此外，母体 DEP 暴露增加了成年雄性而非雌性大脑中的促炎细胞因子白细胞介素-1β（IL-1β）水平，母体 DEP 和 NR 均降低了雄性而非雌性大脑中的抗炎细胞因子白细胞介素-10（IL-10）水平。同样，只有 DEP/NR 雄性显示出先天免疫识别基因 toll 样受体 4（Tlr4）及其下游效应物半胱氨酸天冬氨酸蛋白酶-1（caspase-1）表达增加。
这些结果表明，妊娠晚期母体应激增加了后代（尤其是雄性）对产前空气污染物暴露的有害影响的易感性，这可能是由于这些因素协同作用于先天免疫识别基因和发育中大脑内的下游神经炎症级联反应所致。
