000 03138 am a22006373u 4500
042 _adc
100 1 0 _aManfredi-Lozano, Maria
_eauthor
_91529
700 1 0 _aLeysen, Valerie
_eauthor
700 1 0 _aAdamo, Michela
_eauthor
_91531
700 1 0 _aPaiva, Isabel
_eauthor
_91532
700 1 0 _aRovera, Renaud
_eauthor
_91533
700 1 0 _aPignat, Jean-Michel
_eauthor
_91534
700 1 0 _aTimzoura, Fatima Ezzahra
_eauthor
_91535
700 1 0 _aCandlish, Michael
_eauthor
_91536
700 1 0 _aEddarkaoui, Sabiha
_eauthor
_91537
700 1 0 _aMalone, Samuel A.
_eauthor
_91538
700 1 0 _aSilva, Mauro S. B.
_eauthor
_91539
700 1 0 _aTrova, Sara
_eauthor
_91540
700 1 0 _aImbernon, Monica
_eauthor
700 1 0 _aDecoster, Laurine
_eauthor
_91542
700 1 0 _aCotellessa, Ludovica
_eauthor
_91543
700 1 0 _aTena-Sempere, Manuel
_eauthor
700 1 0 _aClaret, Marc
_eauthor
_91545
700 1 0 _aPaoloni-Giacobino, Ariane
_eauthor
_91546
700 1 0 _aPlassard, Damien
_eauthor
_91547
700 1 0 _aPaccou, Emmanuelle
_eauthor
_91548
700 1 0 _aVionnet, Nathalie
_eauthor
_91549
700 1 0 _aAcierno, James
_eauthor
700 1 0 _aMaceski, Aleksandra Maleska
_eauthor
_91551
700 1 0 _aLutti, Antoine
_eauthor
_91552
700 1 0 _aPfrieger, Frank
_eauthor
_91553
700 1 0 _aRasika, S.
_eauthor
700 1 0 _aSantoni, Federico
_eauthor
700 1 0 _aBoehm, Ulrich
_eauthor
_91556
700 1 0 _aCiofi, Philippe
_eauthor
700 1 0 _aBuée, Luc
_eauthor
_91558
700 1 0 _aHaddjeri, Nasser
_eauthor
_91559
700 1 0 _aBoutillier, Anne-Laurence
_eauthor
_91560
700 1 0 _aKuhle, Jens
_eauthor
_91561
700 1 0 _aMessina, Andrea
_eauthor
700 1 0 _aDraganski, Bogdan
_eauthor
_91563
700 1 0 _aGiacobini, Paolo
_eauthor
700 1 0 _aPitteloud, Nelly
_eauthor
700 1 0 _aPrevot, Vincent
_eauthor
245 0 0 _aGnRH replacement rescues cognition in Down Syndrome
260 _c2022-09-02.
500 _a/pmc/articles/PMC7613827/
500 _a/pubmed/36048943
520 _aCurrently, 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.
540 _a
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nScience
856 4 1 _uhttp://dx.doi.org/10.1126/science.abq4515
_zConnect to this object online.
999 _c1825
_d1825