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GnRH replacement rescues cognition in Down syndrome

dc.rights.licenseopenen_US
dc.contributor.authorMANFREDI-LOZANO, Maria
dc.contributor.authorLEYSEN, Valerie
dc.contributor.authorADAMO, Michela
dc.contributor.authorPAIVA, Isabel
dc.contributor.authorROVERA, Renaud
dc.contributor.authorPIGNAT, Jean-Michel
dc.contributor.authorTIMZOURA, Fatima Ezzahra
dc.contributor.authorCANDLISH, Michael
dc.contributor.authorEDDARKAOUI, Sabiha
dc.contributor.authorMALONE, Samuel A.
dc.contributor.authorSILVA, Mauro S. B.
dc.contributor.authorTROVA, Sara
dc.contributor.authorIMBERNON, Monica
dc.contributor.authorDECOSTER, Laurine
dc.contributor.authorCOTELLESSA, Ludovica
dc.contributor.authorTENA-SEMPERE, Manuel
dc.contributor.authorCLARET, Marc
dc.contributor.authorPAOLONI-GIACOBINO, Ariane
dc.contributor.authorPLASSARD, Damien
dc.contributor.authorPACCOU, Emmanuelle
dc.contributor.authorVIONNET, Nathalie
dc.contributor.authorACIERNO, James
dc.contributor.authorMACESKI, Aleksandra Maleska
dc.contributor.authorLUTTI, Antoine
dc.contributor.authorPFRIEGER, Frank
dc.contributor.authorRASIKA, Sowmyalakshmi
dc.contributor.authorSANTONI, Federico
dc.contributor.authorBOEHM, Ulrich
hal.structure.identifierNeurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]
dc.contributor.authorCIOFI, Philippe
dc.contributor.authorBUEE, Luc
dc.contributor.authorHADDJERI, Nasser
dc.contributor.authorBOUTILLIER, Anne-Laurence
dc.contributor.authorKUHLE, Jens
dc.contributor.authorMESSINA, Andrea
dc.contributor.authorDRAGANSKI, Bogdan
dc.contributor.authorGIACOBINI, Paolo
dc.contributor.authorPITTELOUD, Nelly
dc.contributor.authorPREVOT, Vincent
dc.date.accessioned2023-05-11T14:14:57Z
dc.date.available2023-05-11T14:14:57Z
dc.date.created2022
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/180991
dc.description.abstractEnAt the present time, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive nonreproductive neurological symptoms closely parallel a postpubertal decrease in hypothalamic as well as extrahypothalamic expression of a master molecule that controls reproduction-gonadotropin-releasing hormone (GnRH)- and appear related to an imbalance in a microRNA-gene network known to regulate GnRH neuron maturation together with altered hippocampal synaptic transmission. Epigenetic, cellular, chemogenetic, and pharmacological interventions that restore physiological GnRH levels abolish olfactory and cognitive defects in Ts65Dn mice, whereas pulsatile GnRH therapy improves cognition and brain connectivity in adult DS patients. GnRH thus plays a crucial role in olfaction and cognition, and pulsatile GnRH therapy holds promise to improve cognitive deficits in DS. © 2022 American Association for the Advancement of Science. All rights reserved.
dc.description.sponsorshipVieillissement et démence: un rôle hormonal?en_US
dc.description.sponsorshipDéveloppement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheimeen_US
dc.description.sponsorshipULNEen_US
dc.language.isoENen_US
dc.subject.enTrisomy
dc.subject.enDementia
dc.subject.enIntellectual disability
dc.subject.enCognitive decline
dc.subject.enPreoptic area
dc.subject.enHypothalamic-pituitary-gonadal axis
dc.subject.enAnosmia
dc.subject.enInfertility
dc.subject.enMicroRNA
dc.subject.enOtx2
dc.title.enGnRH replacement rescues cognition in Down syndrome
dc.title.alternativeScienceen_US
dc.typeDocument de travail - Pré-publicationen_US
dc.identifier.doi10.1126/science.abq4515en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed36048943en_US
dc.description.sponsorshipEuropeROLE OF THE TANYCYTIC BARRIER AT THE BLOOD-HYPOTHALAMUS INTERFACE DURING METABOLIC DISORDER DEVELOPMENTen_US
bordeaux.hal.laboratoriesNeurocentre Magendie - U1215en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamRelations glie-neuroneen_US
bordeaux.identifier.funderIDEuropean Research Councilen_US
hal.exportfalse
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.au=MANFREDI-LOZANO,%20Maria&LEYSEN,%20Valerie&ADAMO,%20Michela&PAIVA,%20Isabel&ROVERA,%20Renaud&rft.genre=preprint


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