Characterization of N-methyl- d-aspartate receptors in the hyperammonemic Sparse fur mouse

The N-methyl- d-aspartate (NMDA) receptor, a glutamate receptor subtype, is a ligand-gated ion channel. Overstimulation of NMDA receptors may increase intracellular Ca 2+ concentrations to lethal levels in neurodegenerative disorders affecting the basal ganglia. Such excitotoxicity may also contribute to the loss of medium spiny neurons in the striata of the hyperammonemic sparse fur ( spf/Y) mouse, a model of the X-linked disorder of the urea cycle, ornithine carbamoyltransferase deficiency (OCTD). Levels of quinolinic acid (QA), a potent NMDA agonist, are elevated in the brains of spf/Y mice. Further, direct injection of QA into the striatum produces selective degeneration of medium spiny neurons. Microglia, an endogenous source of QA in the brain, are abundant in spf/Y mice during the period of neuronal degeneration. The location and density of NMDA receptors was visualized by gold labelled immunocytochemistry with a polyclonal antibody to the NMDAR1 receptor subtype and their distribution quantified. A 58% reduction was found in the median density value in the layer V pyramidal neurons in fronto-parietal cortex ( p