ArticleScience (New York, N.Y.)2022
GnRH replacement rescues cognition in Down syndrome.
Registry-linked trialOpen access · greenAbstract read
In one paragraph
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04390646 (Effect of Pulsatile GnRH Therapy on Cognition in Down Syndrome), which is not on this map. Cited by 50 papers.
0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
19.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Pulsatile GnRH Therapy on Cognition in Down Syndrome: Randomized Placebo Control Study
Who cites it
50 citing papers in PubMed, 85 citations in OpenAlex.
- GnRH-receptor antagonism as a targeted approach to reproductive dysfunction in polycystic ovary syndrome.EBioMedicine · 2026Article
- Tanycytes: bloodhounds of the metabolic brain.Trends in endocrinology and metabolism: TEM · 2026Review
- Pubertal development and hypothalamic-pituitary-gonadal axis are altered in male mice lacking Mecp2.Journal of neuroendocrinology · 2026Article
- Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis.Science (New York, N.Y.) · 2026Article
- Integrated Single-Cell and System Network Analysis: Exploring Cellular Communication Network Complexity and Signal Transmission Dysregulation in Down Syndrome Brain.Neuroinformatics · 2026Article
- FSH Signaling in Osteoporosis and Alzheimer's Disease.Current osteoporosis reports · 2026Review
- Structural MRI assessment of hypothalamic alterations and cognitive implications in adolescents with rapid pubertal progression.BMC medical imaging · 2026Article
- Pulsatile Release of Human Gonadotropin Releasing Hormone Using a Photoactivated Depot Containing an Unusual Light Cleaved Functionality.Molecular pharmaceutics · 2026Article
- Unraveling the impact ofBrain communications · 2026Article
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- Targeting FSH for osteoporosis, obesity, and Alzheimer's disease.Trends in molecular medicine · 2025Review
- The neuroscience of cancer: Focus on neuropeptidergic systems.Acta pharmaceutica Sinica. B · 2025Review
- Investigation of a mouse model of Prader-Willi Syndrome with combined disruption of Necdin and Magel2.JCI insight · 2025Article
- GnRH and Cognition.Endocrinology · 2025Review
- Dietary Soy Preserves Cognitive Function in Experimental Fetal Alcohol Spectrum Disorder: Role of Increased Signaling through Notch and Gonadotropin Releasing Hormone Networks.Journal of behavioral and brain science · 2025Article
- The Dynamicity of the Oxytocin Receptor in the Brain May Trigger Sensory Deficits in Autism Spectrum Disorder.Current issues in molecular biology · 2025Review
- Genetics and Epigenetics of Human Pubertal Timing: The Contribution of Genes Associated With Central Precocious Puberty.Journal of the Endocrine Society · 2025Review
- Enduring differential patterns of neuronal loss and myelination along 6-month pulsatile gonadotropin-releasing hormone therapy in individuals with Down syndrome.Brain communications · 2025Article
- Successful treatment of PGAD/GPD with leuprolide: a case report.Frontiers in psychiatry · 2025Article
- Neuroendocrinology of bone.Pituitary · 2024Review
Corrections and comments
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Authors and funding
38 authors at 13 institutions in 5 countries.
Maria Manfredi-Lozano *Univ. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0003-3801-1955
Valerie Leysen *Univ. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.
Michela Adamo *Department of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID 0000-0002-9994-0945
Isabel PaivaLaboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364, Université de Strasbourg-CNRS, Strasbourg, France.ORCID 0000-0001-7607-9390
Renaud RoveraUniversité de Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, Bron, France.ORCID 0000-0002-2017-1451
Jean-Michel PignatDepartment of Clinical Neurosciences, Neurorehabilitation Unit, University Hospital CHUV, Lausanne, Switzerland.
Fatima Ezzahra TimzouraUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0002-0499-9785
Michael CandlishExperimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany.
Sabiha EddarkaouiUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0002-5057-9335
Samuel A MaloneUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0002-6824-6854
Mauro S B SilvaUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0003-4447-6388
Sara TrovaUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0001-9270-4977
Monica ImbernonUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.
Laurine DecosterUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.
Ludovica CotellessaUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0003-1124-576X
Manuel Tena-SempereUniversidad de Córdoba, IMIBC/HURS, CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Córdoba, Spain.ORCID 0000-0002-4741-5567
Marc ClaretNeuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.ORCID 0000-0001-7766-9296
Ariane Paoloni-GiacobinoDepartment of Genetic Medicine, University Hospitals of Geneva, Genève, Switzerland.ORCID 0000-0001-9432-1785
Damien PlassardCNRS UMR 7104, INSERM U1258, GenomEast Platform, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, Illkirch, France.ORCID 0000-0001-8569-6163
Emmanuelle PaccouDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Nathalie VionnetDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID 0000-0002-5420-8216
James AciernoDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.
Aleksandra Maleska MaceskiNeurologic Clinic and Polyclinic, MS Centre and Research Centre for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID 0000-0002-1916-5927
Antoine LuttiLaboratory for Research in Neuroimaging (LREN), Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID 0000-0003-3281-5477
Frank PfriegerCentre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.ORCID 0000-0001-7085-1431
S RasikaUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0001-8733-4641
Federico SantoniFaculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-3258-4747
Ulrich BoehmExperimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, Homburg, Germany.ORCID 0000-0003-2436-6907
Philippe CiofiUniversité de Bordeaux, Inserm, U1215, Neurocentre Magendie, Bordeaux, France.
Luc BuéeUniv. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0002-6261-4230
Nasser HaddjeriUniversité de Lyon, Université Claude Bernard Lyon 1, Inserm, Stem Cell and Brain Research Institute U1208, Bron, France.
Anne-Laurence BoutillierLaboratoire de Neurosciences Cognitives et Adaptatives (LNCA), UMR 7364, Université de Strasbourg-CNRS, Strasbourg, France.ORCID 0000-0002-2317-9280
Jens KuhleNeurologic Clinic and Polyclinic, MS Centre and Research Centre for Clinical Neuroimmunology and Neuroscience Basel, University Hospital Basel, University of Basel, Basel, Switzerland.
Andrea MessinaDepartment of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID 0000-0002-2393-1874
Bogdan DraganskiLaboratory for Research in Neuroimaging (LREN), Centre for Research in Neurosciences, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.ORCID 0000-0002-5159-5919
Paolo Giacobini *Univ. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0002-3075-1441
Nelly Pitteloud *Department of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.ORCID 0000-0003-0971-3237
Vincent Prevot *Univ. Lille, Inserm, CHU Lille, Lille Neuroscience and Cognition, UMR-S 1172, Labex DistAlz, Lille, France.ORCID 0000-0001-7185-3615
Inserm · FRUniversity of Lausanne · CHCentre National de la Recherche Scientifique · FRSaarland University · DEUniversité Claude Bernard Lyon 1 · FRUniversity of Basel · CHCentro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas · ESInstitut des Neurosciences Cellulaires et Intégratives · FRInstituto de Salud Carlos III · ESMax Planck Institute for Human Cognitive and Brain Sciences · DEUniversité de Bordeaux · FRUniversity Hospital of Lausanne · CHUniversity of Geneva · CH
Funding
Swiss National Science Foundation 135679Swiss National Science Foundation 159780
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.
Indexed as
CognitionCognitive DysfunctionDown SyndromeGonadotropin-Releasing HormoneOlfaction DisordersAdultAnimalsDisease Models, AnimalFemaleHumansHypothalamusMaleMiceMiddle AgedSynaptic TransmissionYoung AdultGonadotropin-Releasing Hormone
Identifiers
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Registered trials
NCT04390646ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.