Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?
Is There a Critical Period for the Developmental Neurotoxicity of Low-Level Tobacco Smoke Exposure?
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DOI：
10.1093/toxsci/kfw180
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发表时间：
2017-01-01
影响因子：
3.8
通讯作者：
Seidler, Frederic J.
中科院分区：
文献类型：
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作者：
Slotkin, Theodore A.;Stadler, Ashley;Seidler, Frederic J.
孕期接触二手烟会增加神经发育障碍的风险。我们在大鼠身上评估了烟草烟雾提取物（TSE）是否存在一个关键时期，在此期间它会影响乙酰胆碱和血清素系统的发育，而这两个系统是尼古丁和烟草烟雾不良影响的主要靶点。我们通过给予TSE来模拟二手烟暴露，以使尼古丁浓度达到主动吸烟时的十分之一，并设置了3个不同的、为期10天的时间段：交配前、妊娠早期或妊娠晚期。我们从青春期早期（出生后第30天）开始，一直持续到成年期（第150天），对多个脑区进行了纵向评估。在这3个时间段中的任何一个时间段接触TSE都会损害突触前胆碱能活性，并且由于烟碱型胆碱能受体浓度降低而加剧。尽管在所有3个处理时间段都能看到不良影响，但存在明显的进展过程，交配前暴露的敏感性最低，妊娠期暴露的敏感性更高。血清素受体也因TSE暴露而减少，情况相同：交配前暴露影响较小，妊娠早期暴露影响中等，妊娠晚期暴露影响较大。由于血清素能回路可以抵消胆碱能缺陷的神经行为影响，这些受体变化是适应不良的。因此，低水平烟草烟雾的影响不存在单一的“关键时期”，而是根据暴露时的发育阶段存在不同的敏感性。我们的研究结果强调，不仅在孕期，而且在受孕前的时期，或者一般来说对于育龄妇女，都需要避免接触二手烟。
Secondhand tobacco smoke exposure in pregnancy increases the risk of neurodevelopmental disorders. We evaluated in rats whether there is a critical period during which tobacco smoke extract (TSE) affects the development of acetylcholine and serotonin systems, prominent targets for adverse effects of nicotine and tobacco smoke. We simulated secondhand smoke exposure by administering TSE so as to produce nicotine concentrations one-tenth those in active smoking, with 3 distinct, 10-day windows: premating, early gestation or late gestation. We conducted longitudinal evaluations in multiple brain regions, starting in early adolescence (postnatal day 30) and continued to full adulthood (day 150). TSE exposure in any of the 3 windows impaired presynaptic cholinergic activity, exacerbated by a decrement in nicotinic cholinergic receptor concentrations. Although the adverse effects were seen for all 3 treatment windows, there was a distinct progression, with lowest sensitivity for premating exposure and higher sensitivity for gestational exposures. Serotonin receptors were also reduced by TSE exposure with the same profile: little effect with premating exposure, intermediate effect with early gestational exposure and large effect with late gestational exposure. As serotonergic circuits can offset the neurobehavioral impact of cholinergic deficits, these receptor changes were maladaptive. Thus, there is no single 'critical period' for effects of low-level tobacco smoke but there is differential sensitivity dependent upon the developmental stage at the time of exposure. Our findings reinforce the need to avoid secondhand smoke exposure not only during pregnancy, but also in the period prior to conception, or generally for women of childbearing age.