Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation
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DOI：
10.1016/j.jhep.2009.04.021
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发表时间：
2009-09-01
影响因子：
25.7
通讯作者：
Berry, Elliot M.
中科院分区：
文献类型：
--
作者：
Magen, Iddo;Avraham, Yosefa;Berry, Elliot M.
背景/目标：小鼠内源性大麻素系统在肝毒素诱导的人类肝硬化和肝性脑病（HE）模型中发挥作用。我们现在报告大麻二酚（CBD）（大麻的非精神活性成分）对由胆管结扎（BDL）（慢性肝病模型）引起的HE的治疗作用。结果：结扎组小鼠在八臂迷宫和T迷宫实验中的认知功能以及旷场实验中的运动功能均受到损伤，而CBD可改善这些功能。BDL提高了海马TNF-α-受体1基因的表达，CBD降低了该基因的表达。然而，BDL降低了脑源性神经营养因子（BDNF）基因的表达，CBD增加了该基因的表达。CBD对认知、运动和TNF-α受体1表达的影响可被A（2）A腺苷受体拮抗剂ZM 241385阻断。结论：BDL的作用可能与下调A（2）A腺苷受体有关。CBD通过激活这种受体来逆转这些效应，导致对连接效应的补偿。(C)2009年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease.Methods: CBD (5 mg/kg; i.p.) was administered over 4 weeks to mice that had undergone BDL.Results: Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.Conclusions:The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect. (C) 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.