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首页> 外文期刊>Glia >2-Arachidonoylglycerol Elicits Neuroprotective Effects on Excitotoxically Lesioned Dentate Gyrus Granule Cells via Abnormal-Cannabidiol-Sensitive Receptors on Microglial Cells
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2-Arachidonoylglycerol Elicits Neuroprotective Effects on Excitotoxically Lesioned Dentate Gyrus Granule Cells via Abnormal-Cannabidiol-Sensitive Receptors on Microglial Cells

机译：2-花生四烯酸甘油酯通过对小胶质细胞的异常大麻受体敏感受体对兴奋性损害的齿状回齿状回颗粒细胞产生神经保护作用。

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Endocannabinoids like 2-arachidonoylglycerol (2-AG) exert neuroprotective effects after brain injuries. According to current concepts, these neuroprotective effects are due to interactions between 2-AG and cannabinoid (CB)l receptors on neurons. Moreover, 2-AG modulates migration and pro- liferation of microglial cells which are rapidly activated after brain lesion. This effect is mediated via CB2- and abnormal-cannabidiol (abn-CBD)-sensitive receptors. In the present study, we investigated whether the abn-CBD-sensitive receptor on microglial cells contributes to 2-AG-mediated neuroprotection in organotypic hippocampal slice cultures (OHSCs) after excitotoxic lesion induced by NMDA (50 mu M) application for 4 h. This lesion caused neuronal damage and accumulation of microglial cells within the granule cell layer. To analyze the role of abn-CBD-sensitive receptors for neuroprotection and microglial cell accumulation, two agonists of the abn-CBD-sensitive receptor, abn-CBD or 2-AG, two antagonists, 1,3-dimethoxy-5methyl-2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclo- hexen 1 -yl]-benzene (O-1918) or cannabidiol (CBD), and the CB1 receptor antagonist AM251, were applied to NMDA-lesioned OHSC. Propidium iodide (PI) labeling was used as a marker of degenerating neurons and isolectin B-4 (IB4) as a marker of microglial cells. Application of both, abn-CBD or 2-AG to lesioned OHSC significantly decreased the num ber of IB4+ microglial cells and PI+ neurons in the dentate gyrus. In contrast to AM251, application of O-1918 or CBD antagonized these effects. When microglial cells were depleted by preincubation of OHSC with the bisphosphonate clodronate (100 mu g/mL) for 5 days before excitotoxic lesion, 2-AG and abn-CBD lost their neuroprotective effects. We therefore propose that the endocannabinoid 2-AG exerts its neuroprotective effects via activation of abn-CBD-sensitive receptors on microglial cells. (C) 2008 Wiley-Liss, Inc.
机译：诸如2-花生四烯酰甘油（2-AG）之类的内源性大麻素在脑损伤后发挥神经保护作用。根据当前的概念，这些神经保护作用归因于2-AG与神经元上的大麻素（CB）1受体之间的相互作用。此外，2-AG调节小胶质细胞的迁移和增殖，这些小胶质细胞在脑部病变后迅速被激活。该作用是通过CB2和异常大麻双酚（abn-CBD）敏感受体介导的。在本研究中，我们调查了NMDA（50μM）施用引起的兴奋性毒性损伤4 h后，小胶质细胞上的abn-CBD敏感受体是否有助于2-AG介导的有机型海马切片培养物（OHSCs）中的神经保护。该病变引起神经元损伤和小胶质细胞在颗粒细胞层内的积累。为了分析abn-CBD敏感受体在神经保护和小胶质细胞积累中的作用，研究了abn-CBD敏感受体的两种激动剂，abn-CBD或2-AG，两种拮抗剂，1,3-二甲氧基-5甲基-2-应用[（1R，6R）-3-甲基-6-（1-甲基乙烯基）-2-环己烯1-基]-苯（O-1918）或大麻二酚（CBD）和CB1受体拮抗剂AM251 NMDA损害的OHSC。碘化丙啶（PI）标记用作退化神经元的标记，异凝集素B-4（IB4）用作小胶质细胞的标记。将abn-CBD或2-AG应用于受损的OHSC，可显着降低齿状回中IB4 +小胶质细胞和PI +神经元的数量。与AM251相比，O-1918或CBD的使用可拮抗这些作用。在通过OHSC与双膦酸盐氯膦酸盐（100μg / mL）预温育5天以消除小胶质细胞之前，兴奋性毒性损伤之前，2-AG和abn-CBD失去了神经保护作用。因此，我们提出内源性大麻素2-AG通过激活小胶质细胞上的abn-CBD敏感受体发挥其神经保护作用。 （C）2008 Wiley-Liss，Inc.

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