Mostrar el registro sencillo del ítem
Memory deficits in a juvenile rat model of type 1 diabetes are due to excess 11β-HSD1 activity, which is upregulated by high glucose concentrations rather than insulin deficiency
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
hal.structure.identifier | CHU Bordeaux, Nuclear Medicine, 33604, Pessac, France | |
dc.contributor.author | BROSSAUD, Julie | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | BOSCH-BOUJU, Clémentine | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
hal.structure.identifier | Biologie du fruit et pathologie [BFP] | |
dc.contributor.author | MARISSAL-ARVY, Nathalie | |
hal.structure.identifier | Université de Bordeaux [UB] | |
hal.structure.identifier | CHU Bordeaux, Pediatric Endocrinology and DiaBEA unit, Hôpital des Enfants, 33076 Bordeaux, France | |
dc.contributor.author | CAMPAS-LEBECQUE, Marie-Neige | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | HELBLING, Jean-Christophe | |
hal.structure.identifier | University of Edinburgh [Edin.] | |
dc.contributor.author | WEBSTER, Scott | |
hal.structure.identifier | University of Edinburgh [Edin.] | |
dc.contributor.author | WALKER, Brian | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | FIORAMONTI, Xavier | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | FERREIRA, Guillaume | |
hal.structure.identifier | Université de Bordeaux [UB] | |
hal.structure.identifier | CHU Bordeaux, Pediatric Endocrinology and DiaBEA unit, Hôpital des Enfants, 33076 Bordeaux, France | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | BARAT, Pascal | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
hal.structure.identifier | CHU Bordeaux, Nuclear Medicine, 33604, Pessac, France | |
dc.contributor.author | CORCUFF, Jean-Benoît | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
dc.contributor.author | MOISAN, Marie-Pierre | |
dc.date.issued | 2023-09 | |
dc.identifier.issn | 0012-186X | |
dc.description.abstractEn | Introduction/Aim: Children with diabetes may display cognitive alterations although vascular disorders have not yet appeared. Glucose level variations together with relative insulin deficiency in treated type-1 diabetes (T1D) were reported to impact brain function indirectly through dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. We have recently shown that enhancement of glucocorticoid levels in T1D children is not only dependent on their secretion but also on their tissue concentration, which is linked to 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity. HPA axis dysfunction and memory alteration were further dissected in a juvenile rat model of diabetes showing that excess 11β-HSD1 activity within hippocampus is associated with hippocampal-dependent memory deficits. Here, to investigate the causal relationships between diabetes, 11β-HSD1 activity and hippocampus-dependent memory deficits, we evaluated the beneficial effect of 11β-HSD1 inhibition on hippocampal-related memory in juvenile diabetic rats. Furthermore, we examined whether diabetes-associated enhancement of hippocampal 11β-HSD1 activity is due to an increase of brain glucose concentration and/or a decrease in insulin signaling.Methods/Results: Diabetes was induced in juvenile rats by daily intraperitoneal injection of streptozotocin for 2 consecutive days. Inhibition of 11β-HSD1 was obtained by administrating the compound UE2316 twice daily by gavage for 3 weeks before assessing hippocampal-dependent object location memory. Hippocampal 11β-HSD1 activity was estimated by the ratio of corticosterone:dehydrocorticosterone measured by mass spectrometry. Regulation of 11β-HSD1 activity in response to changes in glucose or insulin levels was determined ex vivo on acute brain hippocampal slices. The insulin regulation of 11β-HSD1 was further examined in vivo using virally-mediated knock-down of insulin receptor expression specifically in the hippocampus. Our data show that inhibiting 11β-HSD1 activity prevents the hippocampal-related memory deficits of diabetic juvenile rats. A significant increase (nearly 50%) of hippocampal 11β-HSD1 activity was found in slices incubated in high glucose condition (13.9 mM) versus normal glucose condition (2.8 mM) without insulin. However, 11β-HSD1 activity was not affected by variations in the insulin concentration either using the hippocampal slices or after decrease of hippocampal insulin receptor expression.Conclusions: Together these data demonstrate that increase of 11β-HSD1 activity contributes to memory deficits observed in juvenile diabetic rats and that excess of hippocampal 11β-HSD1 activity stems from high glucose levels rather than insulin deficiency. 11β-HSD1 might be a therapeutic target to treat cognitive impairments associated with diabetes. | |
dc.language.iso | en | |
dc.publisher | Springer Verlag | |
dc.subject.en | 2.02 Animal -rat, 3.05.08 Diabetes in childhood, 3.05.12 Psychological aspects, 3.06.14 Pathogenic mechanisms, 11β-hydroxysteroid dehydrogenase type 1, glucocorticoids, Abbreviations: T1D, type 1 diabetes 11β-HSD1, 11β-hydroxysteroid dehydrogenase type 1 GC, glucocorticoids DHC, dehydrocorticosterone Cs, corticosterone InsR, Insulin Receptor AAV, N-Methyl-D-glucamine STZ, Object location memory, corticosterone, Insulin Receptor, adeno-associated virus | |
dc.title.en | Memory deficits in a juvenile rat model of type 1 diabetes are due to excess 11β-HSD1 activity, which is upregulated by high glucose concentrations rather than insulin deficiency | |
dc.type | Article de revue | |
dc.identifier.doi | 10.1007/s00125-023-05942-3 | |
dc.subject.hal | Sciences cognitives | |
bordeaux.journal | Diabetologia | |
bordeaux.page | 1735-1747 | |
bordeaux.volume | 66 | |
bordeaux.issue | 9 | |
bordeaux.peerReviewed | oui | |
hal.identifier | hal-04175051 | |
hal.version | 1 | |
hal.popular | non | |
hal.audience | Internationale | |
hal.origin.link | https://hal.archives-ouvertes.fr//hal-04175051v1 | |
bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Diabetologia&rft.date=2023-09&rft.volume=66&rft.issue=9&rft.spage=1735-1747&rft.epage=1735-1747&rft.eissn=0012-186X&rft.issn=0012-186X&rft.au=BROSSAUD,%20Julie&BOSCH-BOUJU,%20Cl%C3%A9mentine&MARISSAL-ARVY,%20Nathalie&CAMPAS-LEBECQUE,%20Marie-Neige&HELBLING,%20Jean-Christophe&rft.genre=article |
Archivos en el ítem
Archivos | Tamaño | Formato | Ver |
---|---|---|---|
No hay archivos asociados a este ítem. |