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J Neurochem ; 80(3): 438-47, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11908465

ABSTRACT

In animal models of diabetes mellitus, such as the streptozotocin-diabetic rat (STZ-rat), spatial learning impairments develop in parallel with a reduced expression of long-term potentiation (LTP) and enhanced expression of long-term depression (LTD) in the hippocampus. This study examined the time course of the effects of STZ-diabetes and insulin treatment on the hippocampal post-synaptic glutamate N-methyl-D-aspartate (NMDA) receptor complex and other key proteins regulating hippocampal synaptic transmission in the post-synaptic density (PSD) fraction. In addition, the functional properties of the NMDA-receptor complex were examined. One month of STZ-diabetes did not affect the NMDA receptor complex. In contrast, 4 months after induction of diabetes NR2B subunit immunoreactivity, CaMKII and Tyr-dependent phosphorylation of the NR2A/B subunits of the NMDA receptor were reduced and alphaCaMKII autophosphorylation and its association to the NMDA receptor complex were impaired in STZ-rats compared with age-matched controls. Likewise, NMDA currents in hippocampal pyramidal neurones measured by intracellular recording were reduced in STZ-rats. Insulin treatment prevented the reduction in kinase activities, NR2B expression levels, CaMKII-NMDA receptor association and NMDA currents. These findings strengthen the hypothesis that altered post-synaptic glutamatergic transmission is related to deficits in learning and plasticity in this animal model.


Subject(s)
Diabetes Mellitus, Experimental/metabolism , Hippocampus/metabolism , Receptors, N-Methyl-D-Aspartate/metabolism , Animals , Blotting, Western , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Central Nervous System Diseases/metabolism , Excitatory Postsynaptic Potentials/physiology , Hippocampus/chemistry , Hippocampus/cytology , Male , Neuronal Plasticity/physiology , Organ Culture Techniques , Phosphorylation , Pyramidal Cells/metabolism , Rats , Rats, Wistar , Receptors, N-Methyl-D-Aspartate/analysis
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