TY  - BOOK
AU  - Manfredi-Lozano,Maria
AU  - Leysen,Valerie
AU  - Adamo,Michela
AU  - Paiva,Isabel
AU  - Rovera,Renaud
AU  - Pignat,Jean-Michel
AU  - Timzoura,Fatima Ezzahra
AU  - Candlish,Michael
AU  - Eddarkaoui,Sabiha
AU  - Malone,Samuel A.
AU  - Silva,Mauro S.B.
AU  - Trova,Sara
AU  - Imbernon,Monica
AU  - Decoster,Laurine
AU  - Cotellessa,Ludovica
AU  - Tena-Sempere,Manuel
AU  - Claret,Marc
AU  - Paoloni-Giacobino,Ariane
AU  - Plassard,Damien
AU  - Paccou,Emmanuelle
AU  - Vionnet,Nathalie
AU  - Acierno,James
AU  - Maceski,Aleksandra Maleska
AU  - Lutti,Antoine
AU  - Pfrieger,Frank
AU  - Rasika,S.
AU  - Santoni,Federico
AU  - Boehm,Ulrich
AU  - Ciofi,Philippe
AU  - Buée,Luc
AU  - Haddjeri,Nasser
AU  - Boutillier,Anne-Laurence
AU  - Kuhle,Jens
AU  - Messina,Andrea
AU  - Draganski,Bogdan
AU  - Giacobini,Paolo
AU  - Pitteloud,Nelly
AU  - Prevot,Vincent
TI  - GnRH replacement rescues cognition in Down Syndrome
PY  - 2022///-09-02
KW  - Text
KW  - local
N1  - /pmc/articles/PMC7613827; /pubmed/36048943
N2  - Currently, no viable treatment exists for cognitive and olfactory deficits in Down syndrome (DS). We show in a DS model (Ts65Dn mice) that these progressive non-reproductive neurological symptoms closely parallel a post-pubertal decrease in hypothalamic as well as extra-hypothalamic expression of a master molecule controlling 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, while 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
UR  - http://dx.doi.org/10.1126/science.abq4515
ER  -