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CBD modulates DNA methylation in the prefrontal cortex and hippocampus of mice exposed to forced swim.

CBD 调节暴露于强迫游泳的小鼠前额叶皮层和海马的 DNA 甲基化。

  • 影响因子:3.16
  • DOI:10.1016/j.bbr.2020.112627
  • 作者列表:"Sales AJ","Guimarães FS","Joca SRL
  • 发表时间:2020-06-18
Abstract

:Cannabidiol (CBD), a non-psychotomimetic component of Cannabis sativa plant, shows therapeutic potential in psychiatric disorders, including depression. The molecular mechanisms underlying the antidepressant-like effects of CBD are not yet understood. Previous studies in differentiated skin cells demonstrated that CBD regulates DNA methylation, an overall repressive epigenetic mechanism. Both stress exposure and antidepressant treatment can modulate DNA methylation in the brain, and lead to gene expression changes associated with depression neurobiology. We investigated herein if the antidepressant effect of CBD could be associated with changes in DNA methylation in the prefrontal cortex (PFC) and hippocampus (HPC) of mice submitted to the forced swimming test (FST). Therefore, we assessed: i) the behavioral effects induced by CBD and DNA methylation inhibitors (DNMTi: 5-AzaD and RG108), alone or in association; ii) the effects induced by CBD and DNMTi in global DNA methylation and DNMT activity, in PFC and HPC. Results showed that treatment with CBD (10 mg/kg), 5-AzaD and RG108 (0.2 mg/kg) induced an antidepressant-like effect in the FST. Similar effects were observed after the combination of sub-effective doses of CBD (7 mg/kg) and 5-AzaD or CBD (7 mg/kg) and RG108 (0.1 mg/kg). Also, stress reduced DNA methylation and DNMT activity in the HPC and increased it in the PFC. CBD and DNMTi treatment prevented these changes in both brain structures. Altogether, our results indicate that CBD regulates DNA methylation in brain regions relevant for depression neurobiology, suggesting that this mechanism could be related to CBD-induced antidepressant effects.

摘要

: 大麻二酚 (CBD) 是大麻植物的非精神模拟成分,在包括抑郁症在内的精神疾病中显示出治疗潜力。CBD 抗抑郁样作用的分子机制尚不清楚。以前在分化的皮肤细胞中的研究表明,CBD 调节 DNA 甲基化,这是一种整体的抑制性表观遗传机制。压力暴露和抗抑郁治疗均可调节大脑中的 DNA 甲基化,并导致与抑郁症神经生物学相关的基因表达变化。我们在此研究了 CBD 的抗抑郁作用是否与前额叶皮质 (PFC) 和海马 (HPC) 中 DNA 甲基化的变化有关提交强制游泳试验 (FST) 的小鼠。因此,我们评估了: i) CBD 和 DNA 甲基化抑制剂 (DNMTi: 5-AzaD 和 RG108) 单独或联合诱导的行为效应; ii) CBD 和 DNMTi 在全局 DNA 甲基化和 DNMT 活性、 PFC 和 HPC 中诱导的效应。结果表明,CBD (10 mg/kg) 、 5-AzaD 和 RG108 (0.2 mg/kg) 治疗可诱导 FST 中的抗抑郁样作用。在组合亚有效剂量的 CBD (7 mg/kg) 和 5-AzaD 或 CBD (7 mg/kg) 和 RG108 (0.1 mg/kg) 后观察到类似的效果。同样,压力降低了 HPC 中的 DNA 甲基化和 DNMT 活性,增加了 PFC 中的 DNA 甲基化和 DNMT 活性。CBD 和 DNMTi 治疗阻止了这两种脑结构的这些变化。总之,我们的研究结果表明,CBD 调节与抑郁症神经生物学相关的脑区 DNA 甲基化,提示该机制可能与 CBD 诱导的抗抑郁作用有关。

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影响因子:5.83
发表时间:2020-01-22
DOI:10.1523/JNEUROSCI.0786-19.2019
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影响因子:6.22
发表时间:2020-01-17
DOI:10.1038/s41386-020-0614-2
作者列表:["Chadha R","Meador-Woodruff JH"]

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