BINDING-PROPERTIES OF GLUTAMATE RECEPTORS IN STREPTOZOTOCIN-INDUCED DIABETES IN RATS

The biochemical mechanisms by which diabetes modulates cognitive funct ion are not well, established. Here, we determined the effects of stre ptozotocin (STZ) administration on the binding properties of alpha-ami no-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-asp artate (NMDA) subtypes of glutamate receptors in rats, using quantitat ive autoradiographic analysis of H-3-AMPA and [H-3]glutamate binding o n brain tissue sections. The STZ injection (70 mg/kg intraperitoneally ) produced a reduction of H-3-AMPA binding in various brain regions, a n effect that is due to a decrease in receptor affinity. The STZ-induc ed reduction of H-3-AMPA binding varied in different brain structures, being more pronounced in the striatum, cerebral cortex, and hippocamp us and almost absent in the cerebellum. Western blots performed on hip pocampal membranes revealed that the decrease in H-3-AMPA binding is p ossibly associated with changes in immunologic properties for one glut amate receptor subunit (GluR1). Finally, the effect of STZ-induced dia betes appeared to be specific to the AMPA subtype of glutamate recepto rs, as the same treatment did not modify [H-3]glutamate binding to NMD A receptors. These changes in AMPA receptor properties may have import ant implications for understanding the biochemical mechanisms underlyi ng cognitive impairment in diabetes.