Polli Filip Souza, Kohlmeier Kristi Anne
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nicotine Tob Res. 2020 Oct 8;22(10):1694-1710. doi: 10.1093/ntr/ntz196.
The World Health Organization (WHO) reported that smoking cessation rates among women have stagnated in the past decade and estimates that hundreds of millions of women will be smokers in the next decade. Social, environmental, and biological conditions render women more susceptible to nicotine addiction, imposing additional challenges to quit smoking during gestation, which is likely why more than 8% of pregnancies in Europe are associated with smoking. In epidemiological investigations, individuals born from gestational exposure to smoking exhibit a higher risk of development of attention-deficit/hyperactive disorder (ADHD) and liability to drug dependence. Among other teratogenic compounds present in tobacco smoke, nicotine actions during neuronal development could contribute to the observed outcomes as nicotine misleads signaling among progenitor cells during brain development. Several experimental approaches have been developed to address the consequences of prenatal nicotine exposure (PNE) to the brain and behavior but, after four decades of studies, inconsistent data have been reported and the lack of consensus in the field has compromised the hypothesis that gestational nicotine exposure participates in cognitive and emotional behavioral deficits.
In this review, we discuss the most commonly used PNE models with focus on their advantages and disadvantages, their relative validity, and how the different technical approaches could play a role in the disparate outcomes.
We propose methodological considerations, which could improve the translational significance of the PNE models.
Such alterations might be helpful in reconciling experimental findings, as well as leading to development of treatment targets for maladaptive behaviors in those prenatally exposed.
In this article, we have reviewed the advantages and disadvantages of different variables of the commonly used experimental models of PNE. We discuss how variations in the nicotine administration methods, the timing of nicotine exposure, nicotine doses, and species employed could contribute to the disparate findings in outcomes for PNE offspring, both in behavior and neuronal changes. In addition, recent findings suggest consideration of epigenetic effects extending across generations. Finally, we have suggested improvements in the available PNE models that could contribute to the enhancement of their validity, which could assist in the reconciliation of experimental findings.
世界卫生组织（WHO）报告称，在过去十年中，女性戒烟率停滞不前，预计在未来十年将有数亿女性成为吸烟者。社会、环境和生物学因素使女性更容易对尼古丁上瘾，这给孕期戒烟带来了额外挑战，这可能就是欧洲超过8%的怀孕与吸烟有关的原因。在流行病学调查中，孕期暴露于吸烟环境中出生的个体患注意力缺陷多动障碍（ADHD）和药物依赖的风险更高。在烟草烟雾中存在的其他致畸化合物中，尼古丁在神经元发育过程中的作用可能导致了上述结果，因为尼古丁在大脑发育过程中误导了祖细胞之间的信号传递。已经开发了几种实验方法来研究产前尼古丁暴露（PNE）对大脑和行为的影响，但经过四十年的研究，报告的数据并不一致，该领域缺乏共识，这削弱了孕期尼古丁暴露参与认知和情感行为缺陷的假说。
在本综述中，我们讨论了最常用的PNE模型，重点关注它们的优缺点、相对有效性，以及不同的技术方法如何在不同的结果中发挥作用。
我们提出了方法学上的考虑因素，这可能会提高PNE模型的转化意义。
这种改变可能有助于协调实验结果，并为产前暴露个体的适应不良行为开发治疗靶点。
在本文中，我们回顾了常用的PNE实验模型不同变量的优缺点。我们讨论了尼古丁给药方法、尼古丁暴露时间、尼古丁剂量和所使用物种的变化如何导致PNE后代在行为和神经元变化方面的不同结果。此外，最近的研究结果表明需要考虑跨代的表观遗传效应。最后，我们建议改进现有的PNE模型，这可能有助于提高其有效性，从而有助于协调实验结果。
