Ultrastructural Localization of Neuronal Brain CB2 Cannabinoid Receptors

Ultrastructural Localization of Neuronal Brain CB2 Cannabinoid Receptors
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DOI:
10.1196/annals.1432.037
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发表时间:
2008-01-01
期刊:
DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES
影响因子:
--
通讯作者:
Onaivi, E. S.
Onaivi, E. S.
中科院分区:
其他
文献类型:
--
作者:
Brusco, A.;Tagliaferro, P. A.;Onaivi, E. S.

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大脑中神经元 CB2 大麻素受体 (CB2-Rs) 的功能表达一直存在争议。我们和其他人现在已经证明 CB2-R 在大脑的神经元和神经胶质细胞中表达。然而,这些受体的亚细胞定位尚未得到表征。在这项研究中,我们使用免疫组织化学电子显微镜来确定 CB2-Rs 在两个大脑区域的亚细胞分布。 CA1 海马区和黑质的脑切片进行 CB2-R 免疫染色,并通过电子显微镜进行分析。在每个区域中,在神经元以及神经胶质细胞和内皮细胞中检测到 CB2-R 的免疫过氧化物酶标记。在神经元细胞中,在体细胞和大中型树突中观察到 CB2-R 免疫反应性。在体细胞中,CB2-R标记主要与粗面内质网和高尔基体相关,表明其是内源合成的。在树突中,在细胞质中观察到 CB2-R 标记,并且与轴突末端突触接触区域附近的质膜相关,表明这些受体的突触后分布。在免疫反应性神经胶质细胞和内皮细胞的 CB2R 中,还发现标记与质膜相关。在黑质中,一些无髓鞘轴突对 CB2-R 具有免疫反应性,但我们很少发现 CB2-R 标记的轴突末端。这些结果扩展了我们之前对突触后皮质 CB2-R 的检测,并提供了额外的超微结构证据,表明 CB2-R 主要位于海马 CA1 区和黑质的突触后。 CB2-R 的突触前和/或突触后定位的功能意义仍有待确定。
The functional expression of neuronal CB2 cannabinoid receptors (CB2-Rs) in the brain has been controversial. We and others have now demonstrated that CB2-Rs are expressed in neurons and glial cells in the brain. However, the subcellular localization of these receptors has not been characterized. In this study we used immunohistochemical electron microscopy to determine the subcellular distribution of CB2-Rs in two brain regions. Brain sections from the CA1 hippocampal area and substantia nigra were immunostained for CB2-Rs and analyzed by electron microscopy. In each region immunoperoxidase labeling for CB2-Rs was detected in neurons as well as in glial and endothelial cells. In neuronal cells, CB2-R immunoreactivity was observed in somata and large and medium-sized dendrites. In the soma, the CB2-R labeling was mainly associated with the rough endoplasmic reticulum and Golgi apparatus, suggesting its endogenous synthesis. In the dendrites, the CB2-R labeling was observed in the cytoplasm and was associated with the plasma membrane near the area of synaptic contact with axon terminals, indicating a postsynaptic distribution of these receptors. In CB2Rs in immunoreactive glial and endothelial cells, the labeling was also found to be associated with the plasma membrane. In the substantia nigra, some unmyelinated axons were immunoreactive for CB2-Rs, but we rarely found CB2-R-labeled axon terminals. These results extend our previous detection of postsynaptic cortical CB2-Rs and provide additional ultrastructural evidence that CB2-Rs are mainly postsynaptic in the CA1 area of the hippocampus and substantia nigra. The functional implication of pre- and/or postsynaptic localization of CB2-Rs remains to be determined.