Lauterstein Dana E, Tijerina Pamella B, Corbett Kevin, Akgol Oksuz Betul, Shen Steven S, Gordon Terry, Klein Catherine B, Zelikoff Judith T
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
Genome Technology Center, New York University School of Medicine, New York, NY 10016, USA.
Int J Environ Res Public Health. 2016 Apr 12;13(4):417. doi: 10.3390/ijerph13040417.
Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.
电子烟是一种由电池供电的设备，含有尼古丁、甘油、丙二醇、调味剂和其他物质，其受欢迎程度正在不断上升。由于尼古丁是一种已知的神经毒素，它们对发育中的大脑构成潜在威胁。我们假设，在生命早期接触电子烟会导致中枢神经系统（CNS）转录组发生变化，这些变化与不良神经生物学结果和长期疾病状态相关。为了验证这一假设，怀孕的C57BL/6小鼠在整个妊娠期每天（通过全身吸入）暴露于含有尼古丁（13 - 16毫克/毫升）或不含尼古丁的电子烟产生的气溶胶中（每天3小时；每周5天）；出生后，幼崽和母鼠从出生后第4 - 6天开始在整个哺乳期一起暴露于电子烟气溶胶中，并使用与妊娠期暴露相同的暴露条件。暴露后，从约1个月大的雄性和雌性后代中切除额叶皮质，并通过RNA测序（RNA-Seq）分析基因表达。治疗组之间的比较显示，除尼古丁外的电子烟成分可能部分导致了观察到的生物学效应。两个后代性别和治疗组的转录组改变均与下游不良神经生物学结果显著相关。这项研究的结果表明，生命早期接触电子烟会改变中枢神经系统发育，可能导致慢性神经病理学。
