Increased density of hippocampal kainate receptors but normal density of NMDA and AMPA receptors in a rat model of prenatal protein malnutrition.

Abstract

The postnatal development of excitatory amino acid receptor types including kainate, N-methyl-D-aspartate (NMDA), and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was assessed in the hippocampus, entorhinal cortex, and adjacent neocortex in normal and prenatally protein malnourished rats ages 15, 30, 90, and 220 postnatal days by quantitative autoradiography. Tritiated ligands used to measure binding site density were (3)[H]kainate, (3)[H]MK-801, and (3)[H]AMPA, respectively. Kainate receptors showed statistically significant increases in binding density in stratum lucidum of CA3 (hippocampal mossy fiber zone) in 90- and 220-day-old malnourished rats compared with age- and sex-matched controls but not in 15- or 30-day-old malnourished rats. Compared with previous anatomic studies, these results are mostly in agreement with a significantly decreased hippocampal mossy fiber plexus in 15-, 90-, and 220-day-old rats but not in 30-day-old rats. These results suggested that the increased density of postsynaptic kainate receptors located mainly on proximal apical dendrites of CA3 pyramidal cells may be compensatory to decreased glutamate release due to the reduction in mossy fiber plexus. In contrast, the density of putative NMDA and AMPA receptors quantified in prenatally malnourished rats was comparable to the density quantified in age- and sex-matched control rats, as were all three receptor types in entorhinal cortex and adjacent neocortex. Thus, the selectivity of the compensation of (3)[H]kainate-labeled mossy fiber plexus in adult but not in early postnatal developing malnourished rats may help ensure continued breeding and survival of the species under otherwise adverse environmental conditions.