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GnRH replacement rescues cognition in Down syndrome.

ABSTRACT: 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.

SUBMITTER: Manfredi-Lozano M 

PROVIDER: S-EPMC7613827 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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GnRH replacement rescues cognition in Down syndrome.

Manfredi-Lozano Maria M   Leysen Valerie V   Adamo Michela M   Paiva Isabel I   Rovera Renaud R   Pignat Jean-Michel JM   Timzoura Fatima Ezzahra FE   Candlish Michael M   Eddarkaoui Sabiha S   Malone Samuel A SA   Silva Mauro S B MSB   Trova Sara S   Imbernon Monica M   Decoster Laurine L   Cotellessa Ludovica L   Tena-Sempere Manuel M   Claret Marc M   Paoloni-Giacobino Ariane A   Plassard Damien D   Paccou Emmanuelle E   Vionnet Nathalie N   Acierno James J   Maceski Aleksandra Maleska AM   Lutti Antoine A   Pfrieger Frank F   Rasika S S   Santoni Federico F   Boehm Ulrich U   Ciofi Philippe P   Buée Luc L   Haddjeri Nasser N   Boutillier Anne-Laurence AL   Kuhle Jens J   Messina Andrea A   Draganski Bogdan B   Giacobini Paolo P   Pitteloud Nelly N   Prevot Vincent V  

Science (New York, N.Y.) 20220902 6610

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  ...[more]

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