DISTRIBUTION OF GLUTAMATE-RECEPTOR SUBUNIT PROTEINS GLUR2(4), GLUR5 6/7, AND NMDAR1 IN THE CANINE AND PRIMATE CEREBRAL-CORTEX - A COMPARATIVE IMMUNOHISTOCHEMICAL ANALYSIS/

The distribution of the AMPA, kainate and NMDA glutamate receptor subu nit proteins GluR2(4), GluR5/6/7 and NMDAR1, respectively, were analyz ed in the dog hippocampus and neocortex and compared to macaque monkey s 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 pr oteins were characterized by a more restricted cellular distribution i n the CA1-CA3 fields. In the dog neocortex, the GluR2(4) subunit was f ound 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 pop ulation of medium-to-large layer V pyramidal neurons. Layers II and VI were consistently densely labeled with all three receptor classes, es pecially in the case of the GluR5/6/7 and NMDAR1 subunits. All three a ntibodies used thus far showed an intense labeling of the perikaryon a nd dendritic segments in the dog cerebral cortex. Apical dendrites cou ld be followed through several layers in some cases, and formed well-s tained plexuses in all of the neocortical layers. These patterns were very similar to those observed in the hippocampus and neocortex of bot h monkey and human, although GluR2(4) and NMDAR1 immunoreactivity was visualized in more heterogeneous populations of cortical neurons in th e primates than in dogs. Glutamate is the principal excitatory neurotr ansmitter in the brain and is involved in the excitotoxic mechanisms o ccurring in pathologic conditions such as epilepsy and cerebral ischem ia. The dog has been shown to represent a reliable large animal model for several neurologic disorders and is used particularly in investiga tions of the cerebral repercussions of cardiac arrest. The overall sim ilarity of the staining patterns in dogs and primates observed in the present study suggest that the dog model may be highly valuable for th e characterization of potential cellular and synaptic shifts in the di stribution and expression of specific glutamate receptor subunits, in the context of other biochemical and morphologic effects of global bra in ischemia and reperfusion following cardiac arrest.