大麻二酚对大鼠大脑皮层、下丘脑和脑桥中H3K4Me3、H3K9ac、H3K9Me2、H3K27Me3和H3K36Me2翻译后修饰影响的初步研究

José Carlos Pastrana-Trejo, Fátima Duarte-Aké, Rosa Us-Camas, Clelia De-la-Peña, Linda Parker, Roger G Pertwee, Eric Murillo-Rodríguez
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引用次数: 6

摘要

背景:大麻二酚(CBD)是大麻中的一种非精神药物成分,通过调节几种病理状况,包括疼痛、癫痫、自闭症等,显示出治疗前景。然而,CBD的分子作用机制尚不清楚,最近的数据表明CBD的核元素的作用,如组蛋白活性的参与。目的:本研究评价CBD (20 mg/Kg/i.p)给药后大鼠多个脑区组蛋白H3K4Me3、H3K9ac、H3K9Me2、H3K27Me3和H3K36Me2翻译后修饰(PTM)的变化。目的:探讨cbd对大鼠大脑皮层、下丘脑和脑桥组织中H3K4Me3、H3K9ac、H3K9Me2、H3K27Me3和H3K36Me2水平的影响。方法:10只成年大鼠随机分为对照组和CBD (20 mg/Kg/i.p)组。治疗后处死动物,取脑进行大脑皮质、下丘脑和脑桥解剖。采用Western blot方法检测各组蛋白H3K4Me3、H3K9ac、H3K9Me2、H3K27Me3和H3K36Me2的PTM水平。结果:CBD增加了大脑皮层组蛋白H3K4Me3、H3K9ac和H3K27Me3的PTM水平,而H3K9Me2和H3K36Me2无显著差异。此外,在下丘脑中,CBD降低了H3K9ac的含量,而在H3K4Me3、H3K9Me2、H3K27Me3和H3K36Me2中没有观察到显著的影响。最后,在脑桥中,CBD处理大鼠的H3K4Me3的PTM水平显著下降,而H3K9ac、H3K9Me2、H3K27Me3和H3K36Me2的PTM水平无统计学差异。结论:本研究表明,CBD诱导PTM水平对不同脑区组蛋白H3K4Me3、H3K9ac、H3K9Me2、H3K27Me3和H3K36Me2的差异影响。
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Effects on the Post-translational Modification of H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 Levels in Cerebral Cortex, Hypothalamus and Pons of Rats after a Systemic Administration of Cannabidiol: A Preliminary Study.

Background: Cannabidiol (CBD), a non-psychotropic constituent of Cannabis sativa, has shown therapeutic promises by modulating several pathological conditions, including pain, epilepsy autism, among others. However, the molecular mechanism of action of CBD remains unknown and recent data suggest the engagement on CBD´s effects of nuclear elements, such as histone activity.

Aim: This study assessed the changes in the post-translational modification (PTM) on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 in several brain regions of rats after the administration of CBD (20 mg/Kg/i.p.).

Objective: To evaluate the effects on the PTM of histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 levels in the cerebral cortex, hypothalamus and pons of CBD-treated rats.

Methods: Ten adult rats were randomly assigned into 2 groups: Control or CBD (20 mg/Kg/i.p). Animals were sacrificed after treatments and brains were collected for dissections of the cerebral cortex, hypothalamus and pons. Samples were analyzed for PTM on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 levels by Western blot procedure.

Results: CBD increased the PTM levels on the histones H3K4Me3, H3K9ac, and H3K27Me3 in the cerebral cortex whereas no significant differences were found in H3K9Me2 and H3K36Me2. In addition, in the hypothalamus, CBD decreased the contents of H3K9ac while no significant effects were observed in H3K4Me3, H3K9Me2, H3K27Me3, and H3K36Me2. Lastly, in the pons, CBD- treated rats showed a significant decline on the PTM levels of H3K4Me3 whereas no statistical differences were found in H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2.

Conclusion: The study showed that CBD induced differential effects in levels of PTM on the histones H3K4Me3, H3K9ac, H3K9Me2, H3K27Me3, and H3K36Me2 in several brain regions.

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来源期刊
Central nervous system agents in medicinal chemistry
Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology
CiteScore
2.10
自引率
0.00%
发文量
21
期刊介绍: Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.
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