Direct Effects of Nicotine on Cranial Growth and Development

在这里，我们试图了解胎儿和出生后尼古丁暴露对颅面生长和 发展。这一领域意义重大，因为我们对香烟的伴随影响有很好的了解 对出生缺陷进行了研究，但很少有工作专注于尼古丁等个别成分。电子学 香烟现在在没有监管的情况下进入市场，并以安全的名义在市场上销售。AS~11%的孕妇 女性在怀孕期间继续吸烟，电子烟或尼古丁替代疗法可能 被认为是吸烟的更安全的替代品。然而，我们对尼古丁影响的理解， 香烟、电子烟和尼古丁替代疗法之间的共同成分，在 发育中的胎儿，尤其是头面部骨骼发育不良。吸烟与罹患癌症的风险增加有关。 头面部出生缺陷，颅缝早闭。颅骨融合症发生在1：1800-2500名活产儿中，可以 目前有无数的内科并发症，包括眼球突出，颅内压升高，改变 颅骨体积和智力低下。大多数确诊的病例需要神经外科手术来矫正畸形和 恢复正常的增长轨迹。目前尚不清楚尼古丁是否单独增加了颅缝闭锁的风险，但 尼古丁受体最近在头盖骨(缝合)的生长部位被发现。在这里我们的目标是 确定宫内和出生后尼古丁暴露的剂量和暴露方式的影响 阐明1)尼古丁是否可以改变颅面生长；2)是否存在剂量隔离效应；以及3)是否存在 胎儿或婴儿最容易受到这些影响的易感窗口。 该项目的两个调查领域是： 1)描述宫内和产后(哺乳)尼古丁暴露对颅面生长的影响。 我们将利用我们的临床前颅面生长模型来确定尼古丁在一定剂量下的影响。 举止。由于我们之前已经在头骨的生长部位发现了尼古丁受体，我们预计 增加暴露剂量和暴露时间将导致胎儿和出生后生长的可测量的变化 暴露的动物。 2)确定尼古丁对颅骨生长部位、缝合线细胞的影响。 尼古丁是一种已知对细胞新陈代谢有影响的强效兴奋剂。在这里，我们将利用收集的细胞 从缝合判断特定效果(增殖、凋亡、自噬、成骨、衰老) 因为接触尼古丁而引发的。此外，我们还将确定其对尼古丁受体表达的影响 尼古丁暴露的直接目标。

Here we seek to understand the direct effects of fetal and postnatal nicotine exposure on craniofacial growth and development. This area is significant as our knowledge of the concomitant effects of cigarettes have been well studied for birth defects, but little work has focused on the individual components such as nicotine. Electronic cigarettes have now entered the market without regulation and are being marketed as safe. As ~11% of pregnant women continue to smoke during pregnancy, electronic cigarettes or nicotine replacement therapies may be viewed as a safer alternative to cigarette smoking. However, our understanding of the effects of nicotine, the common component between cigarettes, electronic cigarettes, and nicotine replacement therapies, on the developing fetus, specifically the craniofacial skeleton, is poor. Smoking has been linked to an increased risk for the craniofacial birth defect, craniosynostosis. Craniosynostosis occurs in 1:1800-2500 live births and can present with a myriad of medical comorbidities including ocular proptoses, increased intracranial pressure, alter cranial volume, and mental retardation. Most diagnosed cases require neurosurgery to correct the deformity and restore normal growth trajectories. It is unknown if nicotine alone increases the risk for craniosynostosis, but nicotinic receptors have recently been identified within the growth sites of the calvaria (sutures). Here we aim to determine the effects of in utero and postnatal nicotine exposure in a dose by time of exposure manner to elucidate 1) if nicotine can alter craniofacial growth; 2) if there is a segregating effect by dose; and 3) if there is a window of susceptibility during which the fetus or infant would be most susceptible to these effects. The two areas of investigation of this project are: 1) Characterize the effect of in utero and postnatal (lactation) nicotine exposure on craniofacial growth. We will utilize our preclinical craniofacial growth model to determine the effects of nicotine in a dose by time manner. As we have previously identified nicotinic receptors within the growth sites of the skull we anticipate that increasing dose and time of exposure will result in measurable alterations in growth in our fetal and post-natal exposed animals. 2) Define the effects of nicotine on the cells of the cranial growth sites, the sutures. Nicotine is a potent stimulant drug known to have effects on cell metabolism. Here we will utilize cells garnered from the suture to determine the specific effect (proliferation, apoptosis, autophagy, osteogenesis, senescence) precipitated by nicotine exposure. In addition, we will determine the effect on nicotinic receptor expression a direct target of nicotine exposure.