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Δ9 -Tetrahydrocannabinol promotes oligodendrocyte development and CNS myelination in vivo.
Glia ( IF 6.2 ) Pub Date : 2020-09-21 , DOI: 10.1002/glia.23911
Alba Huerga-Gómez 1, 2, 3 , Tania Aguado 1, 2, 3 , Aníbal Sánchez-de la Torre 1, 2, 3 , Ana Bernal-Chico 2, 4, 5 , Carlos Matute 2, 4, 5 , Susana Mato 2, 4, 5, 6 , Manuel Guzmán 1, 2, 3 , Ismael Galve-Roperh 1, 2, 3 , Javier Palazuelos 1, 2, 3
Affiliation  

Δ9‐Tetrahydrocannabinol (THC), the main bioactive compound found in the plant Cannabis sativa, exerts its effects by activating cannabinoid receptors present in many neural cells. Cannabinoid receptors are also physiologically engaged by endogenous cannabinoid compounds, the so‐called endocannabinoids. Specifically, the endocannabinoid 2‐arachidonoylglycerol has been highlighted as an important modulator of oligodendrocyte (OL) development at embryonic stages and in animal models of demyelination. However, the potential impact of THC exposure on OL lineage progression during the critical periods of postnatal myelination has never been explored. Here, we show that acute THC administration at early postnatal ages in mice enhanced OL development and CNS myelination in the subcortical white matter by promoting oligodendrocyte precursor cell cycle exit and differentiation. Mechanistically, THC‐induced‐myelination was mediated by CB1 and CB2 cannabinoid receptors, as demonstrated by the blockade of THC actions by selective receptor antagonists. Moreover, the THC‐mediated modulation of oligodendroglial differentiation relied on the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, as mTORC1 pharmacological inhibition prevented the THC effects. Our study identifies THC as an effective pharmacological strategy to enhance oligodendrogenesis and CNS myelination in vivo.

中文翻译:

Δ9 -Tetrahydrocannabinol 在体内促进少突胶质细胞发育和 CNS 髓鞘形成。

Δ 9-四氢大麻酚 (THC),在植物大麻中发现的主要生物活性化合物,通过激活存在于许多神经细胞中的大麻素受体来发挥其作用。大麻素受体也在生理上与内源性大麻素化合物(即所谓的内源性大麻素)结合。具体来说,内源性大麻素 2-花生四烯酸甘油已被强调为胚胎阶段和脱髓鞘动物模型中少突胶质细胞 (OL) 发育的重要调节剂。然而,从未探索过 THC 暴露对产后髓鞘形成关键时期 OL 谱系进展的潜在影响。在这里,我们表明,在小鼠出生后早期的急性 THC 给药通过促进少突胶质细胞前体细胞周期的退出和分化,增强了皮层下白质的 OL 发育和 CNS 髓鞘形成。从机制上讲,THC 诱导的髓鞘形成是由 CB 介导的1和 CB 2大麻素受体,如选择性受体拮抗剂阻断 THC 作用所证明的那样。此外,THC 介导的少突胶质细胞分化调节依赖于哺乳动物雷帕霉素复合物 1 (mTORC1) 信号通路的激活,因为 mTORC1 药理学抑制阻止了 THC 作用。我们的研究确定 THC 是一种有效的药理学策略,可在体内增强少突胶质细胞生成和 CNS 髓鞘形成。
更新日期:2020-09-21
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