A cannabinoid analogue of Delta9-tetrahydrocannabinol disrupts neural development in chick.

A cannabinoid analogue of Delta9-tetrahydrocannabinol disrupts neural development in chick.
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Delta9-四氢大麻酚的大麻素类似物会破坏小鸡的神经发育。

DOI:
10.1002/bdrb.20166
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发表时间:
2008
期刊:
Birth defects research. Part B, Developmental and reproductive toxicology
影响因子:
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通讯作者:
Finnell,RichardH
Finnell,RichardH
中科院分区:
--
文献类型:
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作者:
Psychoyos,Delphine;Hungund,Basalingappa;Cooper,Thomas;Finnell,RichardH

文献摘要

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避孕药是孕妇最常滥用的非法药物。它的主要精神活性成分Δ9-THC(Δ9-四氢大麻酚)穿过胎盘并在胎儿中积累,可能会损害其发育。在人类中,怀孕早期使用大麻与流产、胎儿酒精样综合征以及后代的学习障碍、记忆障碍和多动症有关。20世纪70年代的经典研究已经得出了关于大麻素在动物模型中的致畸作用的不同结论。此外,关于Δ9-THC对早期胚胎发生的直接影响知之甚少。我们使用鸡胚作为模型,以表征水溶性Δ9-THC类似物O-2545对早期发育的影响。在原肠胚形成时将胚胎暴露于药物(0.035至0.35 mg/ml),并在相当于9-14体节的阶段评估形态缺陷。我们报告O-2545会损害大脑、心脏、体节和脊髓原基的形成。暴露于药物后较短的孵育时间表明,O-2545干扰头部过程和神经板形成的初始步骤。我们的研究结果表明,大麻素O-2545在早期胚胎发育过程中的管理结果在胚胎毒性作用,并用于照亮大麻暴露在怀孕的第二周,在大多数妇女不知道自己怀孕的时间点的风险。出生缺陷研究(部分B)83:477-488,2008。© 2008 Wiley利斯公司
Marijuana is the most commonly abused illicit drug by pregnant women. Its major psychoactive constituent, Δ9‐THC (Δ9‐tetrahydrocannabinol), crosses the placenta and accumulates in the fœtus, potentially harming its development. In humans, marijuana use in early pregnancy is associated with miscarriage, a fetal alcohol‐like syndrome, as well as learning disabilities, memory impairment, and ADHD in the offspring. Classical studies in the 1970 s have reached disparate conclusions as to the teratogenic effects of cannabinoids in animal models. Further, there is very little known about the immediate effects of Δ9‐THC on early embryogenesis. We have used the chick embryo as a model in order to characterize the effects of a water‐soluble Δ9‐THC analogue, O‐2545, on early development. Embryos were exposed to the drug (0.035 to 0.35 mg/ml) at gastrulation and assessed for morphological defects at stages equivalent to 9–14 somites. We report that O‐2545 impairs the formation of brain, heart, somite, and spinal cord primordia. Shorter incubation times following exposure to the drug show that O‐2545 interferes with the initial steps of head process and neural plate formation. Our results indicate that the administration of the cannabinoid O‐2545 during early embryogenesis results in embryotoxic effects and serves to illuminate the risks of marijuana exposure during the second week of pregnancy, a time point at which most women are unaware of their pregnancies.Birth Defects Res (Part B)83:477–488, 2008. © 2008 Wiley‐Liss, Inc.