Department of Pharmaceutical Sciences, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.
Department of Drug Discovery and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, South Carolina, USA.
Eur J Neurosci. 2022 Sep;56(6):4705-4719. doi: 10.1111/ejn.15780. Epub 2022 Aug 30.
Smoking remains the leading cause of preventable death in the United States, with 87% of smokers starting before the age of 18. Age of initiation is a major predictive factor for smoking frequency and successful smoking cessation. People who initiate smoking during adolescences are 2.33 times more likely to become heavy smokers and half as likely to quit compared with smokers who started during adulthood. Additionally, schizophrenia, a disease state linked to altered neurodevelopment during adolescence, is a major predictive factor for smoking status. Smoking rates among people suffering from schizophrenia are between 60% and 90%. Interestingly, the Neuregulin Signalling Pathway (NSP), which plays an important role in neurodevelopment, is implicated in both schizophrenia and nicotine use disorder. Specifically, SNPS in neuregulin 3 (Nrg3) and Erb-B2 Receptor Tyrosine Kinase 4 (ErbB4) have been associated with smoking cessation outcomes and schizophrenia. Here, we examine the effects of chronic nicotine (18 mg/kg/day) and 24-h withdrawal on NSP gene expression in the hippocampus of adult (20-week-old) and adolescent (4-week-old) mice. We show that withdrawal from chronic nicotine decreased the expression of Erbb4 mRNA in the hippocampus of the adult mice but increased the expression of cytosolic Erbb4 protein in adolescent mice. Nrg3 mRNA and protein expression was not altered by chronic nicotine or withdrawal in the adult or adolescent cohorts, but Nrg3 mRNA and synaptosomal protein expression was lower in the adult withdrawal group when compared with their adolescent counterparts. These results highlight the age-specific effects of nicotine withdrawal on the NSP and may contribute to the lower quit rate and higher cigarette consumption of smokers who initiation during adolescences.
吸烟仍然是美国可预防死亡的主要原因，87%的吸烟者在 18 岁之前开始吸烟。起始年龄是预测吸烟频率和成功戒烟的主要因素。在青少年时期开始吸烟的人成为重度吸烟者的可能性是成年人的 2.33 倍，而成功戒烟的可能性则是成年人的一半。此外，精神分裂症是一种与青少年时期神经发育改变相关的疾病状态，也是预测吸烟状况的主要因素。患有精神分裂症的人的吸烟率在 60%至 90%之间。有趣的是，在神经发育中发挥重要作用的神经调节蛋白信号通路（NSP）与精神分裂症和尼古丁使用障碍都有关。具体来说，神经调节蛋白 3（Nrg3）和表皮生长因子受体酪氨酸激酶 4（ErbB4）中的 SNPS 与戒烟结果和精神分裂症有关。在这里，我们研究了慢性尼古丁（18mg/kg/天）和 24 小时戒断对成年（20 周龄）和青少年（4 周龄）小鼠海马体 NSP 基因表达的影响。我们发现，慢性尼古丁戒断降低了成年小鼠海马体中 Erbb4 mRNA 的表达，但增加了青少年小鼠中海马体中细胞溶质 Erbb4 蛋白的表达。Nrg3 mRNA 和蛋白质表达不受成年或青少年队列中慢性尼古丁或戒断的影响，但与青少年对照组相比，成年戒断组的 Nrg3 mRNA 和突触体蛋白表达较低。这些结果突出了尼古丁戒断对 NSP 的年龄特异性影响，可能导致青少年时期开始吸烟的人戒烟率较低和香烟消耗量较高。
