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电子烟气溶胶暴露致孕鼠后代的神经炎症和行为学结局。

Neuroinflammatory and Behavioral Outcomes Measured in Adult Offspring of Mice Exposed Prenatally to E-Cigarette Aerosols.

机构信息

Program in Neuroscience and Behavior, Department of Psychology and Education, Mount Holyoke College, South Hadley, Massachusetts, USA.

Department of Environmental Medicine, New York University School of Medicine, New York, New York, USA.

出版信息

Environ Health Perspect. 2020 Apr;128(4):47006. doi: 10.1289/EHP6067. Epub 2020 Apr 15.

DOI:10.1289/EHP6067
PMID:32293200
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7228099/
Abstract

BACKGROUND

In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus.

OBJECTIVE

The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes.

METHODS

Pregnant female CD-1 mice were randomly assigned to one of three treatment groups () and exposed daily to either filtered air, propylene glycol and vegetable glycerol (50:50 PG/VG vehicle), or to PG/VG with nicotine (). Whole-body exposures were carried out for 3 h/d, 7 d/week, from gestational day (GD)0.5 until GD17.5. Adult male and female offspring (8 weeks old) were assessed across a battery of behavioral assessments followed by region-specific quantification of brain cytokines using multiplex immunoassays.

RESULTS

Adult offspring of both sexes exposed to exhibited elevated locomotor activity in the elevated plus maze and altered stress-coping strategies in the forced swim task. Moreover, male and female offspring exposed to PG/VG with and without nicotine had a 5.2% lower object discrimination score in the novel object recognition task. In addition to differences in offspring behavior, maternal e-cigarette exposure with nicotine led to a reduction in interleukin (IL)-4 and interferon-gamma () in the diencephalon, as well as lower levels of hippocampal (females only). E-cigarette exposure without nicotine resulted in a 2-fold increase of IL-6 in the cerebellum.

DISCUSSION

These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.

摘要

背景

为了降低传统香烟的吸烟率,电子烟(e-cigarettes)被提议作为一种有效的戒烟工具。然而,人们对其毒理学影响知之甚少。这令人担忧,因为在怀孕期间,无论是对母亲还是胎儿来说,电子烟的使用被认为比传统香烟的危害小。

目的

本研究旨在测试母体电子烟使用对成年后代行为和神经免疫结果的神经发育后果。

方法

将怀孕的 CD-1 小鼠随机分配到三个处理组()之一,并每天暴露于过滤空气、丙二醇和蔬菜甘油(50:50 PG/VG 载体)或 PG/VG 加尼古丁()中。全身暴露于 3 小时/天,每周 7 天,从妊娠第 0.5 天(GD0.5)到妊娠第 17.5 天。对成年雄性和雌性后代(8 周龄)进行一系列行为评估,然后使用多重免疫分析定量大脑细胞因子。

结果

暴露于 的雄性和雌性成年后代在高架十字迷宫中表现出更高的运动活性,并在强迫游泳任务中改变了应激应对策略。此外,暴露于 PG/VG 加和不加尼古丁的雄性和雌性后代在新物体识别任务中的物体辨别分数低 5.2%。除了后代行为的差异外,母体电子烟暴露加尼古丁导致间脑中白细胞介素(IL)-4 和干扰素-γ()减少,以及海马体中 (仅雌性)水平降低。电子烟暴露不加尼古丁导致小脑中 IL-6 增加 2 倍。

讨论

这些发现支持电子烟暴露对小鼠模型神经发育的先前不良发现,并为母体电子烟暴露在怀孕期间对成年后代的持续不良行为和神经免疫后果提供了充分的证据。https://doi.org/10.1289/EHP6067.

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