Distribution of glutamate receptor subunit proteins G1uR2(4), GluR5/6/7, and NMDAR1 in the canine and primate cerebral cortex: a comparative immunohistochemical analysis

Abstract

The distribution of the AMPA, kainate and NMDA glutamate receptor subunit proteins G1uR2(4), G1uR5/6/7 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 G1uR5/6/7 subunit proteins were characterized by a more restricted cellular distribution in the CA1-CA3 fields. In the dog neocortex, the G1uR2(4) subunit was found in a higher number of neurons in layers III and V compared to the G1uR5/6/7 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 G1uR5/6/7 and NMDARI 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 G1uR2(4), and NMDARI 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.