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Scientific article
English

GnRH replacement rescues cognition in Down syndrome

Published inScience, vol. 377, no. 6610, eabq4515
Publication date2022-09-02
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.

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Citation (ISO format)
MANFREDI-LOZANO, Maria et al. GnRH replacement rescues cognition in Down syndrome. In: Science, 2022, vol. 377, n° 6610, p. eabq4515. doi: 10.1126/science.abq4515
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ISSN of the journal0036-8075
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