title: NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats.
abstract: OBJECTIVE
  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 alpha-calcium-calmodulin-dependent kinase II. Receptor subunits alphaCaMKII-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 alphaCaMKII 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 alphaCaMKII 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 alphaCaMKII activity and NR2B levels.
  
  
  CONCLUSIONS
  N-Methyl-D-Aspartate receptor expression and phosphorylation is possibly involved in behavioural and electrophysiological abnormalities observed in streptozotocin-diabetic rats.
authors.affiliation: Institute of Pharmacological Sciences, University of Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Luca
authors.forename: L
authors.initials: L
authors.lastname: Ruts
authors.forename: F
authors.initials: F
authors.lastname: Gardoni
authors.forename: F
authors.initials: F
authors.lastname: Cattabeni
authors.forename: G J
authors.initials: GJ
authors.lastname: Biessels
authors.forename: W H
authors.initials: WH
authors.lastname: Gispen
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D010766:Phosphorylation; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D007328:Insulin; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases