Liu Fei, Tao Xinrong, Pang Gang, Wu Diqing, Hu Yuting, Xue Song, Liu Jing, Li Bing, Zhou Li, Liu Qiang, Zhang Yong-Mei
Center for Medical Research, School of Medicine, Anhui University of Science and Technology, Huainan, China.
Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Anhui University of Science and Technology, Huainan, China.
Front Pharmacol. 2020 Jan 22;10:1569. doi: 10.3389/fphar.2019.01569. eCollection 2019.
Cigarette smoking or nicotine exposure during pregnancy is associated with numerous obstetrical, fetal, and developmental complications, as well as an increased risk of adverse health consequences in the adult offspring. In this study, we examined the effects of maternal nicotine exposure during perinatal and lactation stages on behavioral performance and hippocampal neurogenesis in the adolescent stage of offspring mice. Female C57BL/mice received nicotine in drinking water (200 μg/ml nicotine) or vehicle (1% saccharin) starting from 2 weeks premating until the offspring were weaned on postnatal day 20. Experiments started on postnatal day 35. Female offspring with maternal nicotine exposure presented an increase in anxiety-like behavior in an open-field test. BrdU assay revealed that nicotine offspring presented an increase in cell proliferation in hippocampal dentate gyrus, but the number of BrdU cells was decreased in one week and further decreased in three weeks. The occurrence of disarray of DCX cells increased in both male and female nicotine offspring. The density of microglial marker protein Iba1 was significantly increased in the nicotine offspring. Furthermore, the expression of microglia marker Iba1, the CX3CL1, CX3CR1, and downstream molecules PKA and p-ErK were significantly increased in the nicotine group. In summary, maternal nicotine exposure affects both hippocampal neurogenesis and microglial activity in the adolescent offspring.
孕期吸烟或接触尼古丁与众多产科、胎儿及发育并发症相关，同时成年后代出现不良健康后果的风险也会增加。在本研究中，我们检测了围产期和哺乳期母体接触尼古丁对后代小鼠青春期行为表现及海马神经发生的影响。雌性C57BL/小鼠从交配前2周开始饮用含尼古丁的水（200μg/ml尼古丁）或溶剂对照（1%糖精），直至后代在出生后第20天断奶。实验于出生后第35天开始。母体接触尼古丁的雌性后代在旷场试验中表现出焦虑样行为增加。BrdU检测显示，接触尼古丁的后代海马齿状回细胞增殖增加，但BrdU细胞数量在1周时减少，3周时进一步减少。雄性和雌性接触尼古丁的后代中，双皮质素（DCX）细胞排列紊乱的发生率均增加。接触尼古丁的后代中，小胶质细胞标志物蛋白Iba1的密度显著增加。此外，尼古丁组中小胶质细胞标志物Iba1、CX3CL1、CX3CR1及下游分子PKA和磷酸化细胞外信号调节激酶（p-ErK）的表达均显著增加。总之，母体接触尼古丁会影响青春期后代的海马神经发生和小胶质细胞活性。
