Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis
Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis
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DOI：
10.1523/jneurosci.4814-06.2007
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发表时间：
2007-02-28
影响因子：
5.3
通讯作者：
Romero, Julian
中科院分区：
文献类型：
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作者：
Benito, Cristina;Romero, Juan Pablo;Romero, Julian
越来越多的证据支持大麻素化合物对多发性硬化症（MS）治疗有益的观点。然而，大多数实验数据来自MS动物模型。我们研究了MS患者脑组织样本中大麻素CB1和CB2受体和脂肪酸酰胺水解酶（FAAH）酶的状态。脱髓鞘区域被确定并分为活动性、慢性和非活动性斑块。采用免疫组织化学和免疫荧光检测CB1和CB2受体、FAAH密度和细胞表达位点。在MS样品中，大麻素CB1受体在皮质神经元、少突胶质细胞和少突胶质细胞前体细胞中表达，使用双免疫荧光分别证明了针对CB1受体的抗体和针对2型微管相关蛋白、髓鞘碱性蛋白和血小板衍生生长因子受体- α的抗体。CB1受体也存在于巨噬细胞和浸润的t淋巴细胞中。相反，CB2受体存在于MS斑块的t淋巴细胞、星形胶质细胞、血管周围和反应性小胶质细胞（主要组织相容性复合体ii类阳性）中。具体而言，cb2阳性的小胶质细胞均匀分布在活动性斑块内，但位于慢性活动性斑块的周围。FAAH的表达仅限于神经元和肥大星形胶质细胞。与其他神经炎症疾病一样，大麻素CB1和CB2受体以及FAAH酶的选择性胶质表达在MS中被诱导，从而支持内源性大麻素系统在该疾病的发病和/或演变中的作用。
Increasing evidence supports the idea of a beneficial effect of cannabinoid compounds for the treatment of multiple sclerosis (MS). However, most experimental data come from animal models of MS. We investigated the status of cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase (FAAH) enzyme in brain tissue samples obtained from MS patients. Areas of demyelination were identified and classified as active, chronic, and inactive plaques. CB1 and CB2 receptors and FAAH densities and cellular sites of expression were examined using immunohistochemistry and immunofluorescence. In MS samples, cannabinoid CB1 receptors were expressed by cortical neurons, oligodendrocytes, and also oligodendrocyte precursor cells, demonstrated using double immunofluorescence with antibodies against the CB1 receptor with antibodies against type 2 microtubule-associated protein, myelin basic protein, and the platelet-derived growth factor receptor-alpha, respectively. CB1 receptors were also present in macrophages and infiltrated T-lymphocytes. Conversely, CB2 receptors were present in T-lymphocytes, astrocytes, and perivascular and reactive microglia (major histocompatibility complex class-II positive) in MS plaques. Specifically, CB2-positive microglial cells were evenly distributed within active plaques but were located in the periphery of chronic active plaques. FAAH expression was restricted to neurons and hypertrophic astrocytes. As seen for other neuroinflammatory conditions, selective glial expression of cannabinoid CB1 and CB2 receptors and FAAH enzyme is induced in MS, thus supporting a role for the endocannabinoid system in the pathogenesis and/or evolution of this disease.