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 | Unité de Psychoneuroimmunologie, Nutrition et Génétique [PsyNuGen] | |
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 | Unité de recherche génomique et physiologie de la lactation [GPL] | |
hal.structure.identifier | Unité de Psychoneuroimmunologie, Nutrition et Génétique [PsyNuGen] | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
hal.structure.identifier | Nutrition et Neurobiologie intégrée [NutriNeuro] | |
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.contributor.editor | Springer | |
dc.date.accessioned | 2024-06-07T02:04:30Z | |
dc.date.available | 2024-06-07T02:04:30Z | |
dc.date.issued | 2023-06-10 | |
dc.identifier.issn | 0012-186X | |
dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/200329 | |
dc.description.abstractEn | Aims/hypothesis Children with diabetes may display cognitive alterations although vascular disorders have not yet appeared.Variations in glucose levels together with relative insulin deficiency in treated type 1 diabetes have been reported to impactbrain function indirectly through dysregulation of the hypothalamus–pituitary–adrenal axis. We have recently shown thatenhancement of glucocorticoid levels in children with type 1 diabetes is dependent not only on glucocorticoid secretion butalso on glucocorticoid tissue concentrations, which is linked to 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity.Hypothalamus–pituitary–adrenal axis dysfunction and memory alteration were further dissected in a juvenile rat model ofdiabetes showing that excess 11β-HSD1 activity within the hippocampus is associated with hippocampal-dependent memorydeficits. Here, to investigate the causal relationships between diabetes, 11β-HSD1 activity and hippocampus-dependentmemory deficits, we evaluated the beneficial effect of 11β-HSD1 inhibition on hippocampal-related memory in juvenilediabetic rats. We also examined whether diabetes-associated enhancement of hippocampal 11β-HSD1 activity is due to anincrease in brain glucose concentrations and/or a decrease in insulin signalling.Methods Diabetes was induced in juvenile rats by daily i.p. injection of streptozotocin for 2 consecutive days. Inhibitionof 11β-HSD1 was obtained by administrating the compound UE2316 twice daily by gavage for 3 weeks, after whichhippocampal-dependent object location memory was assessed. Hippocampal 11β-HSD1 activity was estimated by the ratioof corticosterone/dehydrocorticosterone measured by LC/MS. Regulation of 11β-HSD1 activity in response to changes inglucose or insulin levels was determined ex vivo on acute brain hippocampal slices. The insulin regulation of 11β-HSD1 wasfurther examined in vivo using virally mediated knockdown of insulin receptor expression specifically in the hippocampus.Results Our data show that inhibiting 11β-HSD1 activity prevents hippocampal-related memory deficits in diabetic juvenile rats.A significant increase (53.0±9.9%) in hippocampal 11β-HSD1 activity was found in hippocampal slices incubated in high glucoseconditions (13.9 mmol/l) vs normal glucose conditions (2.8 mmol/l) without insulin. However, 11β-HSD1 activity was not affectedby variations in insulin concentration either in the hippocampal slices or after a decrease in hippocampal insulin receptor expression.Conclusions/interpretation Together, these data demonstrate that an increase in 11β-HSD1 activity contributes to memory deficitsobserved in juvenile diabetic rats and that an excess of hippocampal 11β-HSD1 activity stems from high glucose levels ratherthan insulin deficiency. 11β-HSD1 might be a therapeutic target for treating cognitive impairments associated with diabetes. | |
dc.language.iso | en | |
dc.publisher | Springer Verlag | |
dc.rights.uri | http://hal.archives-ouvertes.fr/licences/copyright/ | |
dc.subject.en | Glucocorticoids | |
dc.subject.en | 11β-Hydroxysteroid dehydrogenase | |
dc.subject.en | Type 1 diabetes | |
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 du Vivant [q-bio] | |
bordeaux.journal | Diabetologia | |
bordeaux.page | 1735-1747 | |
bordeaux.volume | 66 | |
bordeaux.hal.laboratories | Biologie du Fruit & Pathologie (BFP) - UMR 1332 | * |
bordeaux.issue | 9 | |
bordeaux.institution | Université de Bordeaux | |
bordeaux.institution | INRAE | |
bordeaux.peerReviewed | oui | |
hal.identifier | hal-04602078 | |
hal.version | 1 | |
hal.popular | non | |
hal.audience | Internationale | |
hal.origin.link | https://hal.archives-ouvertes.fr//hal-04602078v1 | |
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