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有读书笔记有附件Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD

聚焦生物 添加于 2012-12-26 21:45 | 3004 次阅读 | 0 个评论

  •  作 者

    Han J, Kesner P, Metna-Laurent M, Duan T, Xu L, Georges F, Koehl M, Abrous DN, Mendizabal-Zubiaga J, Grandes P, Liu Q, Bai G, Wang W, Xiong L, Ren W, Marsicano G, Zhang X

  •  摘 要

    Impairment of working memory is one of the most important deleterious effects of marijuana intoxication in humans, but its underlying mechanisms are presently unknown. Here, we demonstrate that the impairment of spatial working memory (SWM) and in vivo long-term depression (LTD) of synaptic strength at hippocampal CA3-CA1 synapses, induced by an acute exposure of exogenous cannabinoids, is fully abolished in conditional mutant mice lacking type-1 cannabinoid receptors (CB(1)R) in brain astroglial cells but is conserved in mice lacking CB(1)R in glutamatergic or GABAergic neurons. Blockade of neuronal glutamate N-methyl-D-aspartate receptors (NMDAR) and of synaptic trafficking of glutamate alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid receptors (AMPAR) also abolishes cannabinoid effects on SWM and LTD induction and expression. We conclude that the impairment of working memory by marijuana and cannabinoids is due to the activation of astroglial CB(1)R and is associated with astroglia-dependent hippocampal LTD in vivo.

  •  详细资料

    • 关键词: Animals; Astrocytes/*metabolism; Cannabinoids/*pharmacology; Cannabis/chemistry; Hippocampus/cytology/*metabolism; Long-Term Synaptic Depression/drug effects; Memory, Short-Term/*drug effects; Mice; Neuronal Plasticity; Rats; Receptor, Cannabinoid, CB1/genetics/*metabolism
    • 文献种类:期刊
    • 期刊名称: Cell
    • 期刊缩写: Cell
    • 期卷页: 2012年  第148卷 第5期 1039-1050页
    • 地址: College of Life Sciences and Key Laboratory of Modern Teaching Technology, Shaanxi Normal University, Xian, China
    • ISBN: 0092-8674

  • 相关链接 DOI URL 

  •  附 件

    PDF附件Acute cannabinoids impair working memory through astroglial CB1 receptor modulation of hippocampal LTD 

  •  聚焦生物 的文献笔记  订阅

    来自陕西师范大学等多个机构的张遐教授的实验团队的研究人员报道了大麻如何损害大脑记忆功能的作用机理，这为失忆研究提出的新观点，也有助于分析大麻在缓 解疼痛方面的机理研究。在这篇文章中，研究人员通过小鼠实验，发现了大麻作用于工作记忆的分子奥秘就在于星形胶质细胞，研究人员发现仅大脑星形胶质细胞缺 乏CB1R的小鼠，不会受到THC摄入造成的空间工作记忆损伤障碍，而神经细胞中缺乏CB1R的小鼠则会出现病症，这也就是说，假如不同细胞类型表达不同 CB1R，那么就有可能通过激活神经细胞中的受体，而不激活星形胶质细胞中的受体，而达到治疗效果。 这项研究也进一步说明了星形胶质细胞也许在除了空间工作记忆以外的其它形式记忆中，扮演了未知的作用。
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