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hiPSC-Based Model of Prenatal Exposure to Cannabinoids: Effect on Neuronal Differentiation.
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-06-09 , DOI: 10.3389/fnmol.2020.00119
Cláudia C Miranda 1 , Tiago Barata 1 , Sandra H Vaz 2 , Carla Ferreira 3, 4 , Alexandre Quintas 3, 4 , Evguenia P Bekman 1, 2, 5
Affiliation  

Phytocannabinoids are psychotropic substances ofcannabis with the ability to bind endocannabinoid (eCB) receptors that regulate synaptic activity in the central nervous system (CNS). Synthetic cannabinoids (SCs) are synthetic analogs of Δ9-tetrahydrocannabinol (Δ9-THC), the psychotropic compound of cannabis, acting as agonists of eCB receptor CB1. SC is an easily available and popular alternative to cannabis, and their molecular structure is always changing, increasing the hazard for the general population. The popularity of cannabis and its derivatives may lead, and often does, to a child’s exposure to cannabis both in utero and through breastfeeding by a drug-consuming mother. Prenatal exposure to cannabis has been associated with an altered rate of mental development and significant changes in nervous system functioning. However, the understanding of mechanisms of its action on developing the human CNS is still lacking. We investigated the effect of continuous exposure to cannabinoids on developing human neurons, mimicking the prenatal exposure by drug-consuming mother. Two human induced pluripotent stem cells (hiPSC) lines were induced to differentiate into neuronal cells and exposed for 37 days to cannabidiol (CBD), Δ9-THC, and two SCs, THJ-018 and EG-018. Both Δ9-THC and SC, at 10 μM, promote precocious neuronal and glial differentiation, while CBD at the same concentration is neurotoxic. Neurons exposed to Δ9-THC and SC show abnormal functioning of voltage-gated calcium channels when stimulated by extracellular potassium. In sum, all studied substances have a profound impact on the developing neurons, highlighting the importance of thorough research on the impact of prenatal exposure to natural and SC.



中文翻译:

基于hiPSC的大麻素产前暴露模型:对神经元分化的影响。

植物大麻素是大麻的精神药物,具有结合调节中枢神经系统(CNS)突触活性的内源性大麻素(eCB)受体的能力。合成大麻素(SCS)是Δ的合成类似物9四氢大麻酚(Δ 9 -THC),所述精神的大麻化合物,用作ECB受体CB激动剂1。SC是大麻的一种容易获得且流行的替代品,其分子结构始终在变化,从而增加了对普通人群的危害。大麻及其衍生物的流行可能并经常导致儿童接触大麻在子宫内以及吸食毒品的母亲的母乳喂养。产前接触大麻与精神发育速度改变和神经系统功能发生重大变化有关。但是,仍然缺乏对其发展人类中枢神经系统作用机制的理解。我们研究了持续暴露于大麻素对发育中的人类神经元的影响,模仿了吸毒母亲产前的暴露。两种人类诱导多能干细胞(的hiPSC)系诱导分化成神经元细胞,并暴露37天到大麻二酚(CBD),Δ 9 -THC和两个的SC,THJ-018和EG-018。两个Δ 9-10μM的-THC和SC促进早熟的神经元和神经胶质细胞分化,而相同浓度的CBD具有神经毒性。暴露于Δ神经元9时通过细胞外钾刺激-THC和SC显示电压门控钙通道的功能异常。总而言之,所有研究的物质对发育中的神经元都有深远的影响,突显了对产前暴露于自然和SC的影响进行彻底研究的重要性。

更新日期:2020-07-06
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