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大麻二酚通过 Cb1 信号触发的 Akt 和 Erk 通路促进神经元分化。

Cannabidiol Promotes Neuronal Differentiation Using Akt and Erk Pathways Triggered by Cb1 Signaling.

机构信息

IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy.

Department of Pharmaceutical Sciences, University of Eastern Piedmont, Largo Donegani 2, 28100 Novara, Italy.

出版信息

Molecules. 2022 Sep 1;27(17):5644. doi: 10.3390/molecules27175644.

DOI:10.3390/molecules27175644
PMID:36080415
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9457834/
Abstract

Recently, the scientific community has started to focus on the neurogenic potential of cannabinoids. The phytocompound cannabidiol (CBD) shows different mechanism of signaling on cannabinoid receptor 1 (CB1), depending on its concentration. In this study, we investigated if CBD may induce in vitro neuronal differentiation after treatment at 5 µM and 10 µM. For this purpose, we decided to use the spinal cord × neuroblastoma hybrid cell line (NSC-34) because of its proliferative and undifferentiated state. The messenger RNAs (mRNAs) expression profiles were tested using high-throughput sequencing technology and Western blot assay was used to determine the number of main proteins in different pathways. Interestingly, the treatment shows different genes associated with neurodifferentiation statistically significant, such as Rbfox3, Tubb3, Pax6 and Eno2. The CB1 signaling pathway is responsible for neuronal differentiation at 10 µM, as suggested by the presence of p-ERK and p-AKT, but not at 5 µM. A new correlation between CBD, neurodifferentiation and retinoic acid receptor-related orphan receptors (RORs) has been observed.

摘要

最近,科学界开始关注大麻素的神经发生潜力。植物化合物大麻二酚(CBD)在依赖于其浓度的情况下,在大麻素受体 1(CB1)上显示出不同的信号传导机制。在这项研究中,我们研究了 CBD 是否可以在 5 µM 和 10 µM 处理后诱导体外神经元分化。为此,我们决定使用脊髓×神经母细胞瘤杂交细胞系(NSC-34),因为它处于增殖和未分化状态。信使 RNA(mRNA)表达谱使用高通量测序技术进行测试,Western blot 测定用于确定不同途径中的主要蛋白质数量。有趣的是,治疗显示与神经分化相关的不同基因具有统计学意义,例如 Rbfox3、Tubb3、Pax6 和 Eno2。CB1 信号通路负责 10 µM 时的神经元分化,如存在 p-ERK 和 p-AKT 所示,但在 5 µM 时则不然。观察到 CBD、神经分化和视黄酸受体相关孤儿受体(RORs)之间的新关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b95c/9457834/cb1254dc3c87/molecules-27-05644-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b95c/9457834/ab11b033895c/molecules-27-05644-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b95c/9457834/9bd206f2b167/molecules-27-05644-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b95c/9457834/aed1b0989b37/molecules-27-05644-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b95c/9457834/6fe59c2b9866/molecules-27-05644-g004.jpg
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