Fetal exposure to methamphetamine in utero stimulates development of serotonergic neurons in three-dimensional reaggregate tissue culture.
Fetal exposure to methamphetamine in utero stimulates development of serotonergic neurons in three-dimensional reaggregate tissue culture.
复制标题
胎儿在子宫内接触甲基苯丙胺会刺激三维重新聚集组织培养物中血清素能神经元的发育。
DOI：
10.1002/syn.10026
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Heller,Alfred
中科院分区：
文献类型：
--
作者：
Won,Lisa;Bubula,Nancy;Heller,Alfred
甲基苯丙胺是一种具有潜在神经毒性的强效精神运动兴奋剂，被育龄女性广泛滥用，引起了胎儿接触该药物的严重公共卫生问题。目前的研究旨在利用胎儿中脑和纹状体细胞制备的三维重新聚集组织培养物来确定母亲服用甲基苯丙胺对单胺能神经元发育的影响。在这种培养系统中，多巴胺能和血清素能中脑纹状体投射被重建并以与体内观察到的相似的时间过程发展。从妊娠第 6-13 天开始，对怀孕的 C57Bl/6J 小鼠每天注射两次 40 mg/kg 甲基苯丙胺或生理盐水。妊娠第 14 天，来自甲基苯丙胺和暴露于盐水的胚胎的细胞被用来制备重新聚集培养物。在培养第 14 天、29 天、43 天和 64 天时监测重新聚集体和培养基中神经递质及其代谢物的水平。与用盐水处理的胚胎制备的重新聚集体相比，由暴露于甲基苯丙胺的胚胎制备的重新聚集体在所有培养年龄中显示出血清素水平显着升高。在来自暴露于药物的胚胎的 14 天和 29 天培养物中，重新聚集体和培养基中的 5-HIAA 水平也有所升高。多巴胺能黑质纹状体投射的发育对子宫内反复接触甲基苯丙胺具有抵抗力。相比之下，胎儿在妊娠早期到中期接触甲基苯丙胺，会对培养物中血清素的发育产生持久的刺激作用。突触 43:139–144, 2002。© 2001 Wiley-Liss, Inc.
Methamphetamine is a potent psychomotor stimulant with neurotoxic potential which is widely abused by females of childbearing age, raising serious public health concerns in terms of exposure of the fetus to the drug. The current study was conducted to determine the effect of maternal administration of methamphetamine on developing monoaminergic neurons using three‐dimensional reaggregate tissue cultures prepared from fetal mesencephalic and striatal cells. In this culture system, the dopaminergic and serotonergic mesencephalic‐striatal projections are reconstructed and develop with a time course similar to that observed in vivo. Pregnant C57Bl/6J mice were injected twice daily with 40 mg/kg methamphetamine or saline from gestational days 6–13. On gestational day 14, cells from methamphetamine and saline‐exposed embryos were used to prepare reaggregate cultures. Levels of neurotransmitters and their metabolites in the reaggregates and culture medium were monitored at 14, 29, 43, and 64 days of culture. Reaggregates prepared from methamphetamine‐exposed embryos showed a significant elevation in serotonin levels at all culture ages compared to reaggregates prepared from saline‐treated embryos. Levels of 5‐HIAA in reaggregates and culture medium were also elevated in 14‐ and 29‐day‐old cultures derived from drug‐exposed embryos. The development of the dopaminergic nigrostriatal projection was resistant to repeated in utero exposure to methamphetamine. In contrast, exposure of the fetus to methamphetamine, during early to midgestation, produced a long‐lasting stimulatory effect on serotonergic development in culture. Synapse 43:139–144, 2002. © 2001 Wiley‐Liss, Inc.