GnRH replacement rescues cognition in Down syndrome - Archive ouverte HAL Access content directly
Journal Articles Science Year : 2022

GnRH replacement rescues cognition in Down syndrome

Ulrich Boehm


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.
Fichier principal
Vignette du fichier
2022_Manfredi_GnRH.pdf (2.96 Mo) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

inserm-03841247 , version 1 (12-02-2024)




Maria Manfredi-Lozano, Valerie Leysen, Michela Adamo, Isabel Paiva, Renaud Rovera, et al.. GnRH replacement rescues cognition in Down syndrome. Science, 2022, 377 (6610), pp.eabq4515. ⟨10.1126/science.abq4515⟩. ⟨inserm-03841247⟩
95 View
14 Download



Gmail Mastodon Facebook X LinkedIn More