Modulation of cell adhesion systems by prenatal nicotine exposure in limbic brain regions of adolescent female rats
Modulation of cell adhesion systems by prenatal nicotine exposure in limbic brain regions of adolescent female rats
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DOI：
10.1017/s1461145710000179
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发表时间：
2011-03-01
影响因子：
4.8
通讯作者：
Li, Ming D.
中科院分区：
文献类型：
--
作者：
Cao, Junran;Dwyer, Jennifer B.;Li, Ming D.
母亲在怀孕期间吸烟（MS）对后代有长期的神经行为影响。许多MS相关的精神疾病开始或改变在青春期，一个时期的中枢神经系统的持续发展。然而，潜在的分子机制在很大程度上是未知的。鉴于细胞粘附分子（CAM）调节各种神经递质系统，并与许多精神疾病，我们假设，CAM改变了产前治疗的尼古丁，烟草中的主要精神活性成分，在青少年的大脑。从妊娠第4天到第18天，通过渗透微型泵对妊娠Sprague道利大鼠进行尼古丁（3 mg/kg.d）或盐水治疗。雌性后代在出生后第35天被处死，几个边缘脑区（尾壳核，丘脑核，前额叶皮层，杏仁核）进行了解剖，使用微阵列和定量RT-PCR技术的基因表达的评价。各种CAM包括neurexin，免疫球蛋白，钙粘蛋白，和粘附GPCR超家族，和他们的细胞内信号转导通路被修改妊娠尼古丁治疗（GN）。在CAM相关通路中，GN对细胞骨架重组通路的影响比对基因转录通路的影响更大。这些影响是高度区域依赖性的，尾壳核表现出最大的脆弱性。鉴于CAM在神经元发育和突触可塑性中的重要作用，我们的研究结果表明，CAM的改变有助于与MS相关的神经行为缺陷。此外，我们的研究强调，低剂量的尼古丁会在大脑中产生实质性和持久的变化，这意味着怀孕期间的尼古丁替代疗法可能会给后代带来许多与MS相同的风险。
Maternal smoking during pregnancy (MS) has long-lasting neurobehavioural effects on the offspring. Many MS-associated psychiatric disorders begin or change symptomatology during adolescence, a period of continuous development of the central nervous system. However, the underlying molecular mechanisms are largely unknown. Given that cell adhesion molecules (CAMs) modulate various neurotransmitter systems and are associated with many psychiatric disorders, we hypothesize that CAMs are altered by prenatal treatment of nicotine, the major psychoactive component in tobacco, in adolescent brains. Pregnant Sprague Dawley rats were treated with nicotine (3 mg/kg.d) or saline via osmotic mini-pumps from gestational days 4 to 18. Female offspring at postnatal day 35 were sacrificed, and several limbic brain regions (the caudate putamen, nucleus accumbens, prefrontal cortex, and amygdala) were dissected for evaluation of gene expression using microarray and quantitative RT-PCR techniques. Various CAMs including neurexin, immunoglobulin, cadherin, and adhesion-GPCR superfamilies, and their intracellular signalling pathways were modified by gestational nicotine treatment (GN). Among the CAM-related pathways, GN has stronger effects on cytoskeleton reorganization pathways than on gene transcription pathways. These effects were highly region dependent, with the caudate putamen showing the greatest vulnerability. Given the important roles of CAMs in neuronal development and synaptic plasticity, our findings suggest that alteration of CAMs contributes to the neurobehavioural deficits associated with MS. Further, our study underscores that low doses of nicotine produce substantial and long-lasting changes in the brain, implying that nicotine replacement therapy during pregnancy may carry many of the same risks to the offspring as MS.