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

Abstract

Moderate disturbances of learning and memory were recognized as a complication of diabetes mellitus in patients. The streptozotocin-diabetic rat, an animal model of insulin-dependent diabetes, shows impairments in spatial memory and in long-term potentiation expression. We have studied the effect of experimental diabetes on expression of post-synaptic glutamate N-Methyl-D-Aspartate ionotropic receptors and of other key proteins regulating synaptic transmission at the post-synaptic compartment. Methods. In situ hybridization and Western blot analysis were used to assess expression and protein concentration of N-Methyl-D-Aspartate receptors and f-calcium-calmodulin-dependent kinase II. Receptor subunits fCaMKII-dependent phosphorylation was studied in post-synaptic densities obtained 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-Aspartate were unchanged in rats with a diabetic duration of 3 months when compared with age-matched control rats. Accordingly, NR1 and NR2A as well as GluR1, GluR2/3, PSD-95 and fCaMKII protein concentrations in post-synaptic densities were the same in both control and diabetic rats, whereas the immunoreactivity for NR2B was reduced by about 40 %. In addition, the activity of fCaMKII on exogenous substrates, such as syntide-2, and the phosphorylation of NR2A/B subunits of N-Methyl-D-Aspartate receptor was reduced in hippocampal post-synaptic densities of streptozotocin-diabetic rats as compared with control rats. Furthermore, we show that insulin intervention for 3 months after diabetic duration partially restored both fCaMKII activity and NR2B levels. Conclusion/interpretation. N-Methyl-D-Aspartate receptor expression and phosphorylation is possibly involved in behavioural and electrophysiological abnormalities observed in streptozotocin-diabetic rats.