Hof P R, Vissavajjhala P, Rosenthal R E, Fiskum G, Morrison J H
Fishberg Research Center for Neurobiology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Brain Res. 1996 Jun 3;723(1-2):77-89. doi: 10.1016/0006-8993(96)00218-1.
The distribution of the AMPA, kainate and NMDA glutamate receptor subunit proteins GluR2(4), GluR5/6/7 and NMDAR1, respectively, were analyzed in the dog hippocampus and neocortex and compared to macaque monkeys and humans. In the dog hippocampus, these glutamate receptor classes exhibited a comparable distribution with few differences in densities of labeled of neurons in the CA1-CA3 fields and in neuropil staining patterns in the dentate gyrus. In particular, the GluR5/6/7 subunit proteins were characterized by a more restricted cellular distribution in the CA1-CA3 fields. In the dog neocortex, the GluR2(4) subunit was found in a higher number of neurons in layers III and V compared to the GluR5/6/7 or NMDAR1 subunits, which were found predominantly in a population of medium-to-large layer V pyramidal neurons. Layers II and VI were consistently densely labeled with all three receptor classes, especially in the case of the GluR5/6/7 and NMDAR1 subunits. All three antibodies used thus far showed an intense labeling of the perikaryon and dendritic segments in the dog cerebral cortex. Apical dendrites could be followed through several layers in some cases, and formed well-stained plexuses in all of the neocortical layers. These patterns were very similar to those observed in the hippocampus and neocortex of both monkey and human, although GluR2(4) and NMDAR1 immunoreactivity was visualized in more heterogeneous populations of cortical neurons in the primates than in dogs. Glutamate is the principal excitatory neurotransmitter in the brain and is involved in the excitotoxic mechanisms occurring in pathologic conditions such as epilepsy and cerebral ischemia. The dog has been shown to represent a reliable large animal model for several neurologic disorders and is used particularly in investigations of the cerebral repercussions of cardiac arrest. The overall similarity of the staining patterns in dogs and primates observed in the present study suggest that the dog model may be highly valuable for the characterization of potential cellular and synaptic shifts in the distribution and expression of specific glutamate receptor subunits, in the context of other biochemical and morphologic effects of global brain ischemia and reperfusion following cardiac arrest.
分别对犬海马体和新皮质中的AMPA、海人酸和NMDA谷氨酸受体亚基蛋白GluR2(4)、GluR5/6/7和NMDAR1的分布进行了分析，并与猕猴和人类进行了比较。在犬海马体中，这些谷氨酸受体类别呈现出类似的分布，在CA1-CA3区域的神经元标记密度以及齿状回的神经毡染色模式方面几乎没有差异。特别是，GluR5/6/7亚基蛋白在CA1-CA3区域的细胞分布更为局限。在犬新皮质中，与GluR5/6/7或NMDAR1亚基相比，GluR2(4)亚基在III层和V层的神经元中数量更多，而GluR5/6/7或NMDAR1亚基主要存在于中到大的V层锥体神经元群体中。II层和VI层始终被所有三种受体类别密集标记，尤其是在GluR5/6/7和NMDAR1亚基的情况下。迄今为止使用的所有三种抗体在犬大脑皮质中均显示出对核周体和树突节段的强烈标记。在某些情况下，顶端树突可以穿过几层，并且在所有新皮质层中形成染色良好的神经丛。这些模式与在猴和人类的海马体和新皮质中观察到的模式非常相似，尽管在灵长类动物中，GluR2(4)和NMDAR1免疫反应性在皮质神经元的异质群体中比在犬中更易观察到。谷氨酸是大脑中的主要兴奋性神经递质，并且参与在诸如癫痫和脑缺血等病理状况中发生的兴奋性毒性机制。犬已被证明是几种神经系统疾病的可靠大型动物模型，尤其用于心脏骤停的脑反应研究。在本研究中观察到的犬和灵长类动物染色模式的总体相似性表明，在心脏骤停后全脑缺血和再灌注的其他生化和形态学影响的背景下，犬模型对于表征特定谷氨酸受体亚基分布和表达中潜在的细胞和突触变化可能具有很高的价值。
