Maternal methamphetamine exposure causes cognitive impairment and alteration of neurodevelopment-related genes in adult offspring mice
Maternal methamphetamine exposure causes cognitive impairment and alteration of neurodevelopment-related genes in adult offspring mice
复制标题
母亲接触甲基苯丙胺会导致成年小鼠的认知障碍和神经发育相关基因的改变
DOI：
10.1016/j.neuropharm.2018.07.024
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发表时间：
2018-09-15
影响因子：
4.7
通讯作者：
Chen, Teng
中科院分区：
文献类型：
--
作者：
Dong, Nan;Zhu, Jie;Chen, Teng
产前药物暴露会改变个体的认知功能，也可能影响其后代对认知障碍的易感性。青少年和育龄妇女中甲基苯丙胺 (METH) 滥用的高发生率提高了确定母亲甲基苯丙胺暴露对后代认知功能影响的重要性。我们假设，母亲接触冰毒会通过破坏与神经发育相关的基因表达来影响子代小鼠的认知行为。在这里，雌性 C57BL/6 小鼠从青春期到成年期间间歇性地接触逐渐增加剂量的冰毒或盐水，然后持续整个怀孕期。有趣的是，雄性后代在新物体识别和莫里斯水迷宫测试中分别表现出短期识别记忆受损和长期空间记忆保留受损，而雌性后代则没有。此外，母亲接触冰毒会改变雄性和雌性后代的神经发育基因，并且在 HPC 和 NAc 区域观察到 12 个雄性和雌性之间差异表达的基因。这些差异表达的基因涉及神经发生、轴突引导、神经元迁移和神经发育回路的突触。我们的观察表明，母亲接触冰毒会导致雄性和雌性小鼠的 HPC 和 NAc 中神经发育相关基因的差异表达模式，这可能是两性不同认知行为表型的基础。 (C) 2018 Elsevier Ltd. 保留所有权利。
Prenatal drug exposure altered cognitive function in individuals, and may also impact their offspring's susceptibility to cognitive impairment. The high incidence of methamphetamine (METH) abuse among adolescents and women of childbearing age elevates the importance to determine the influence of maternal METH exposure on cognitive functions in the descendants. We hypothesized that maternal METH exposure affects cognitive behavior in offspring mice by disrupting gene expression associated with neural development. Here, female C57BL/6 mice were exposed to intermittent escalating doses of METH or saline from adolescence to adulthood, and then continued through pregnancy. Interestingly, male but not female offspring exhibited impaired short-term recognition memory and long-term spatial memory retention in novel object recognition and Morris water maze test respectively. Additionally, maternal METH exposure altered neurodevelopmental genes in both male and female offspring, and 12 differentially expressed genes between male and female were observed in the HPC and NAc regions. These differentially expressed genes are involved in neurogenesis, axon guidance, neuron migration and synapse of neural development circuits. Our observations suggest that maternal METH exposure induced differential expression patterns of neurodevelopment-related genes in the HPC and NAc of male and female mice, which may underlie the different cognitive behavior phenotypes in both genders. (C) 2018 Elsevier Ltd. All rights reserved.