NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats

Aims/hypothesis. Moderate disturbances of learning and memory were recogniz ed as a complication of diabetes mellitus in patients. The streptozotocin-d iabetic rat, an animal model of insulin-dependent diabetes, shows impairmen ts in spatial memory and in long-term potentiation expression. We have stud ied the effect of experimental diabetes on expression of post-synaptic glut amate N-Methyl-D-Aspartate ionotropic receptors and of other key proteins r egulating synaptic transmission at the post-synaptic compartment. Methods. In situ hybridization and Western blot analysis were used to asses s expression and protein concentration of N-Methyl-D-Aspartate receptors an d alpha-calcium-calmodulin-dependent kinase II. Receptor subunits alpha CaM KII-dependent phosphorylation was studied in post-synaptic densities obtain ed from the hippocampus and cortex of control, streptozotocin-diabetic and insulin-treated rats. Results. The transcript levels of NR1 and NR2A subunits of N-Methyl-D-Aspar tate were unchanged in rats with a diabetic duration of 3 months when compa red with age-matched control rats. Accordingly, NR1 and NR2A as well as Glu R1, GluR2/3, PSD-95 and alpha CaMKII protein concentrations in post-synapti c densities were the same in both control and diabetic rats, whereas the im munoreactivity for NR2B was reduced by about 40 %. In addition, the activit y of alpha CaMKII on exogenous substrates, such as syntide-2, and the phosp horylation of NR2A/B subunits of N-Methyl-D-Aspartate receptor was reduced in hippocampal post-synaptic densities of streptozotocin-diabetic rats as c ompared with control rats. Furthermore, we show that insulin intervention f or 3 months after diabetic duration partially restored both aCaMKII activit y and NR2B levels. Conclusion/interpretation. N-Methyl-D-Aspartate receptor expression and pho sphorylation is possibly involved in behavioural and electrophysiological a bnormalities observed in streptozotocin-diabetic rats.