Diabetologia

, Volume 42, Issue 6, pp 693–701 | Cite as

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

  • M. Di Luca
  • L. Ruts
  • F. Gardoni
  • F. Cattabeni
  • G. J. Biessels
  • W. H. Gispen
Article

Abstract

Aims/hypothesis. 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 α-calcium-calmodulin-dependent kinase II. Receptor subunits αCaMKII-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 αCaMKII 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 αCaMKII 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 αCaMKII 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. [Diabetologia (1999) 42: 693–701]

Keywords Synaptic plasticity hippocampus rat CaMKII NMDA receptor long-term potentiation. 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • M. Di Luca
    • 1
  • L. Ruts
    • 2
  • F. Gardoni
    • 1
  • F. Cattabeni
    • 1
  • G. J. Biessels
    • 2
  • W. H. Gispen
    • 2
  1. 1.Institute of Pharmacological Sciences, University of Milan, Milan, ItalyIT
  2. 2.Department of Medical Pharmacology, Rudolf Magnus Institute for Neurosciences, University of Utrecht, Utrecht, The NetherlandsNL

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