GnRH replacement rescues cognition in Down syndrome.
Adult
Animals
Cognition
/ drug effects
Cognitive Dysfunction
/ drug therapy
Disease Models, Animal
Down Syndrome
/ complications
Female
Gonadotropin-Releasing Hormone
/ pharmacology
Humans
Hypothalamus
/ drug effects
Male
Mice
Middle Aged
Olfaction Disorders
/ drug therapy
Synaptic Transmission
/ drug effects
Young Adult
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
02 09 2022
02 09 2022
Historique:
entrez:
1
9
2022
pubmed:
2
9
2022
medline:
9
9
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36048943
doi: 10.1126/science.abq4515
pmc: PMC7613827
mid: EMS156431
doi:
Substances chimiques
Gonadotropin-Releasing Hormone
33515-09-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
eabq4515Subventions
Organisme : Swiss National Science Foundation
ID : 135679
Pays : Switzerland
Organisme : Swiss National Science Foundation
ID : 159780
Pays : Switzerland
Commentaires et corrections
Type : CommentIn
Type : CommentIn
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