MANFREDI-LOZANO, Maria; LEYSEN, Valerie; ADAMO, Michela; PAIVA, Isabel; ROVERA, Renaud; PIGNAT, Jean-Michel; TIMZOURA, Fatima Ezzahra; CANDLISH, Michael; EDDARKAOUI, Sabiha; MALONE, Samuel A.; SILVA, Mauro S. B.; TROVA, Sara; IMBERNON, Monica; DECOSTER, Laurine; COTELLESSA, Ludovica; TENA-SEMPERE, Manuel; CLARET, Marc; PAOLONI-GIACOBINO, Ariane; PLASSARD, Damien; PACCOU, Emmanuelle; VIONNET, Nathalie; ACIERNO, James; MACESKI, Aleksandra Maleska; LUTTI, Antoine; PFRIEGER, Frank; RASIKA, Sowmyalakshmi; SANTONI, Federico; BOEHM, Ulrich; CIOFI, Philippe; BUEE, Luc; HADDJERI, Nasser; BOUTILLIER, Anne-Laurence; KUHLE, Jens; MESSINA, Andrea; DRAGANSKI, Bogdan; GIACOBINI, Paolo; PITTELOUD, Nelly; PREVOT, Vincent

doi:10.1126/science.abq4515

Langue

Document de travail - Pré-publication

Résumé en anglais

At 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.< Réduire

Mots clés en anglais

Trisomy

Dementia

Intellectual disability

Cognitive decline

Preoptic area

Hypothalamic-pituitary-gonadal axis

Anosmia

Infertility

MicroRNA

Otx2

URI

https://oskar-bordeaux.fr/handle/20.500.12278/180991

DOI

http://dx.doi.org/10.1126/science.abq4515

Projet Européen

ROLE OF THE TANYCYTIC BARRIER AT THE BLOOD-HYPOTHALAMUS INTERFACE DURING METABOLIC DISORDER DEVELOPMENT

Project ANR

Vieillissement et démence: un rôle hormonal?
Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime
ULNE

Unités de recherche

Neurocentre Magendie - U1215

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GnRH replacement rescues cognition in Down syndrome