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Implication des corticoïdes et de leurs récepteurs hippocampiques dans les effets rapides et différés du stress sur le rappel mnésique

Abstract : We first showed the peripheral origin of corticosterone after an acute stress administration (electric foot-shocks) using corticosterone binding globulin-deficient mice (Cbg -/-). Then, we intended to determine if the rapid effects of stress on memory retrieval depended on non-genomic mechanisms and in a further step to precise whether such effects are mediated by mineralocorticoid (MR) or glucocorticoid receptors (GR) in the hippocampus. To that aims, we first injected a macromolecular complex of corticosterone (Cort-3CMO-BSA) that cannot cross the cell membrane to assess the involvement of membrane mechanisms. In a second step, we injected 15 minutes before stress delivery either in the dorsal (DH) or ventral (VH) hippocampus the MR antagonist (RU 28318) and GR antagonist (RU 38486) and evaluated memory at 15, 60, 105 and 120 minutes after stress delivery. Indeed, these delays were chosen according to the occurrence of stress-induced corticosterone peaks measured by microdialysis in DH and VH.The main results obtained in this study are: i) Cbg -/- mice are not affected by stress delivery occurring 15 minutes before memory testing, in contrast wild-type control mice which exhibited an important memory retrieval deficit; ii) Similarly, the rapid effects of stress on memory could be prevented by the systemic injection of metyrapone (a corticosterone synthesis inhibitor); iii) We showed that the rapid (15min) deleterious of stress on memory are mediated by membrane receptors, since the injection of Cort-3CMO-BSA in the DH produced similar effects as stress delivery. Moreover, the effect of the Cort-3CMO-BSA complex is not blocked by systemic injection of anisomycin (a protein synthesis inhibitor); iv) In DH, the injection of RU 28318 blocked the deleterious effects of stress when testing occurred 15 min after stress but not for longer delays. In contrast, RU 38486 prevented memory retrieval impairments when performance was evaluated at 60 but not at 105 min after stress. In addition, the opposite pattern was observed in VH since RU 38486 was denied of any effects when injected at 60 min but blocked the stress-induced memory impairments at the 105 min post-stress delay. The involvement of MR and GR receptors and consequently the efficiency of their antagonists seem to depend on the time-course evolutions of stress-induced corticosterone rises within the DH and VH.In conclusion, our study evidenced that acute stress impairs hippocampus-dependent memory retrieval via a switch mechanism involving the MR then GR in DH at shorter delays and then only GR in VH at longer delay.
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Submitted on : Tuesday, October 15, 2013 - 3:38:10 PM
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Rodolphe Dorey. Implication des corticoïdes et de leurs récepteurs hippocampiques dans les effets rapides et différés du stress sur le rappel mnésique. Médecine humaine et pathologie. Université Sciences et Technologies - Bordeaux I, 2013. Français. ⟨NNT : 2013BOR14790⟩. ⟨tel-00873391⟩

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