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在小鼠模型中,早期暴露于电子烟气溶胶后,海马体中的小胶质细胞激活和神经营养因子的基因表达改变。

Microglia Activation and Gene Expression Alteration of Neurotrophins in the Hippocampus Following Early-Life Exposure to E-Cigarette Aerosols in a Murine Model.

机构信息

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987.

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461.

出版信息

Toxicol Sci. 2018 Mar 1;162(1):276-286. doi: 10.1093/toxsci/kfx257.

Abstract

Recent epidemiological data indicate that the popularity of electronic cigarettes (e-cigarettes), and consequently nicotine use, is rising in both adolescent and adult populations. As nicotine is a known developmental neurotoxin, these products present a potential threat for those exposed during early life stages. Despite this, few studies have evaluated the toxicity of e-cigarettes on the developing central nervous system. The goal of this study was to assess neurotoxicity resulting from early-life exposure to electronic cigarette aerosols in an in vivo model. Specifically, studies here focused on neuro-parameters related to neuroinflammation and neurotrophins. To accomplish this, pregnant and neonatal C57BL/6 mice were exposed to aerosols produced from classic tobacco flavor e-cigarette cartridges (with [13 mg/ml] and without nicotine) during gestation (∼3 weeks) and lactation (∼3 weeks) via whole-body inhalation. Exposure to e-cigarette aerosols with and without nicotine caused significant reductions in hippocampal gene expression of Ngfr and Bdnf, as well as in serum levels of cytokines IL-1β, IL-2, and IL-6. Exposure to e-cigarette aerosols without nicotine enhanced expression of Iba-1, a specific marker of microglia, in the cornus ammonis 1 region of the hippocampus. Overall, our novel results indicate that exposure to e-cigarette aerosols, with and without nicotine, poses a considerable risk to the developing central nervous system. Consequently, e-cigarettes should be considered a potential public health threat, especially early in life, requiring further research and policy considerations.

摘要

最近的流行病学数据表明,电子烟(e-cigarettes)的普及程度,以及尼古丁的使用,在青少年和成年人群体中都在上升。由于尼古丁是一种已知的发育神经毒素,这些产品对那些在生命早期阶段接触到的人构成了潜在威胁。尽管如此,很少有研究评估电子烟对发育中中枢神经系统的毒性。本研究的目的是评估在体内模型中早期暴露于电子烟气溶胶对中枢神经系统的神经毒性。具体来说,这里的研究集中在与神经炎症和神经营养因子有关的神经参数上。为了实现这一目标,对妊娠和新生 C57BL/6 小鼠进行了暴露,使其在妊娠期(约 3 周)和哺乳期(约 3 周)通过全身吸入的方式,接触到经典烟草味电子烟墨盒(含[13mg/ml]和不含尼古丁)产生的气溶胶。接触含尼古丁和不含尼古丁的电子烟气溶胶均导致海马体 Ngfr 和 Bdnf 基因表达显著降低,以及血清细胞因子 IL-1β、IL-2 和 IL-6 水平降低。接触不含尼古丁的电子烟气溶胶会增强海马体 CA1 区小胶质细胞特异性标志物 Iba-1 的表达。总的来说,我们的新结果表明,接触含尼古丁和不含尼古丁的电子烟气溶胶对发育中的中枢神经系统构成了相当大的风险。因此,电子烟应被视为一种潜在的公共健康威胁,尤其是在生命早期阶段,需要进一步的研究和政策考虑。

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