Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus.
OBJECTIVE
Recent studies involving electrophysiology and immunolabelling indicate that short-term insulin treatment of hippocampal neurons in culture induces changes in glutamate receptor function, suggesting that this receptor system can be altered on a relatively rapid time scale during diabetic conditions. To investigate this hypothesis, we examined whether brain glutamate receptors and long-term potentiation are altered in the early stages of diabetes mellitus in non-obese diabetic mice, a genetic model of Type I (insulin-dependent) diabetes mellitus.


METHODS
In vitro receptor autoradiography and immunoblotting were used to study the impact of diabetes on brain glutamate receptors. From an electrophysiological point of view, field potential recordings were also examined in area CA1 of hippocampal slices to determine the influence of diabetes on long-term potentiation.


RESULTS
Quantitative autoradiographic analysis revealed enhanced 3H-glutamate binding to several brain regions of diabetes mice, with maximal increases in the cerebral cortex and hippocampus. Saturation kinetics within the cerebral cortex disclosed that this change of 3H-glutamate was possibly due to an increase in the maximal number of N-methyl- D-aspartate binding sites, an interpretation that was corroborated by Western blot analysis of N-methyl- D-aspartate 2A subunits. Impairment in the expression of hippocampal long-term potentiation was also observed in diabetic mice, while the failure to elicit synaptic potentiation was prevented by insulin treatment.


CONCLUSIONS
Because glutamate receptors are thought to be involved in several degenerative processes, our results suggest that up-regulation of these receptors in the early stages of diabetes could represent an important mechanism underlying neurological complications within the brain of diabetic patients.
Valastro
B
B
Department of Chemistry-Biology, University of Quebec at Trois-Rivieres, Canada.
Cossette
J
J
Lavoie
N
N
Gagnon
S
S
Trudeau
F
F
Massicotte
G
G
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D008957:Models, Genetic; D009928:Organ Specificity; D017470:Receptors, Glutamate / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012016:Reference Values; D015854:Up-Regulation
D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate