Up-regulation of glutamate receptors is associated with LTP defects in the early stages of diabetes mellitus
| Autor: | J. Cossette, G. Massicotte, B. Valastro, S. Gagnon, François Trudeau, N. Lavoie |
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| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Long-Term Potentiation AMPA receptor Biology Receptors N-Methyl-D-Aspartate Mice Mice Inbred NOD Reference Values Diabetes mellitus Internal medicine Genetic model Internal Medicine medicine Animals Receptor Models Genetic Insulin Glutamate receptor Brain Long-term potentiation medicine.disease Up-Regulation Disease Models Animal Diabetes Mellitus Type 1 Endocrinology Receptors Glutamate Organ Specificity Autoradiography NMDA receptor |
| Zdroj: | Diabetologia. 45:642-650 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s00125-002-0818-5 |
| Popis: | 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.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.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.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. |
| Databáze: | OpenAIRE |
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