Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex:: A regional and laminar analysis
Immunocytochemical distribution of the cannabinoid CB1 receptor in the primate neocortex:: A regional and laminar analysis
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DOI：
10.1093/cercor/bhj136
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发表时间：
2007-01-01
期刊：
影响因子：
3.7
通讯作者：
Lewis, David A.
中科院分区：
文献类型：
--
作者：
Eggan, Stephen M.;Lewis, David A.
Delta-9-四氢大麻酚（Delta（9）-THC）对高级认知功能有深远的影响，接触Delta（9）-THC与精神分裂症临床特征的出现或恶化有关。这些作用似乎是通过CB 1受体介导的，CB 1受体是大脑中表达的主要大麻素受体。然而，CB 1受体在灵长类动物大脑新皮层区域中介导认知功能的分布尚不清楚。因此，我们研究了免疫细胞化学定位的CB，受体在猕猴和人类的大脑中使用的抗体，特异性地识别的N-或C-末端的CB 1受体。在猴子中，观察到强烈的CB 1免疫反应主要在轴突和终扣。在猴脑的新皮层区域，CB 1-免疫反应（IR）轴突的密度和层状分布表现出相当大的异质性。新皮质关联区域，如前额叶和扣带皮质，表现出较高的密度，并表现出独特的层状模式的CB 1-IR轴突，与初级感觉和运动皮质相比。CB 1-IR轴突的类似区域和层状分布也存在于人类新皮质中。CB 1-IR轴突在人体组织中有更突出的静脉曲张，但这种差异似乎代表了死后效应，因为在未灌注的猴组织中，类似的形态特征随着死后间隔的增加而增加。在灌注猴前额叶皮质的电子显微镜研究中，CB 1免疫反应主要发现在轴突终端，专门形成对称的突触。高密度，独特的层状分布，和本地化的抑制性终端的CB 1受体在灵长类动物高阶协会地区表明，CB，受体可能发挥关键作用的电路，如那些在精神分裂症中受到干扰的认知功能。
Delta-9-tetrahydrocannabinol (Delta(9)-THC) has profound effects on higher cognitive functions, and exposure to Delta(9)-THC has been associated with the appearance or exacerbation of the clinical features of schizophrenia. These actions appear to be mediated via the CB1 receptor, the principal cannabinoid receptor expressed in the brain. However, the distribution of the CB1 receptor in neocortical regions of the primate brain that mediate cognitive functions is not known. We therefore investigated the immunocytochemical localization of the CB, receptor in the brains of macaque monkeys and humans using antibodies that specifically recognize the N- or C-terminus of the CB1 receptor. In monkeys, intense CB1 immunoreactivity was observed primarily in axons and boutons. Across neocortical regions of the monkey brain, CB1-immunoreactive (IR) axons exhibited considerable heterogeneity in density and laminar distribution. Neocortical association regions, such as the prefrontal and cingulate cortices, demonstrated a higher density, and exhibited a unique laminar pattern of CB1-IR axons, compared with primary sensory and motor cortices. Similar regional and laminar distributions of CB1-IR axons were also present in the human neocortex. CB1-IR axons had more prominent varicosities in human tissue, but this difference appeared to represent a postmortem effect as similar morphological features increased in unperfused monkey tissue as a function of postmortem interval. In electron microscopy studies of perfused monkey prefrontal cortex, CB1 immunoreactivity was predominantly found in axon terminals that exclusively formed symmetric synapses. The high density, distinctive laminar distribution, and localization to inhibitory terminals of CB1 receptors in primate higher-order association regions suggests that the CB, receptor may play a critical role in the circuitry that subserves cognitive functions such as those that are disturbed in schizophrenia.