ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03624556 (Pediatric Exploratory Research Study of EGCG Use and Safety), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Pediatric Exploratory Research Study of EGCG Use and Safety (PERSEUS)
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- Meta-Analysis of Down Syndrome Cortical Development Reveals Underdeveloped State of the Science.Frontiers in cellular neuroscience · 2022Pooled it
- A randomized, double-blind, placebo-controlled phase II trial to explore the effects of a GABAJournal of neurodevelopmental disorders · 2022Trial
- A Researcher's guide to rodent models of Down syndrome: Recent insights and translational perspectives.STAR protocols · 2026Review
- The role of GABANeuroscience and biobehavioral reviews · 2026Review
- Alterations in the Components of the GABA-Glutamate System During ZIKV Infection: A Neuroscience Approach.International journal of molecular sciences · 2026Article
- Increased dendritic inhibition of dentate gyrus granule cells in a mouse model of Down syndrome.Frontiers in cellular neuroscience · 2026Article
- Chronic suppression of monoacylglycerol lipase restores adult neurogenesis in the septal but not the temporal DG in Ts65Dn mouse model of Down syndrome.Brain research bulletin · 2026Article
- Altered motor coordination, vocal communication, and cerebellar circuit connectivity in mice carrying a near-complete human chromosome 21.Translational psychiatry · 2025Article
- Trisomy 21 Alters Motor Coordination, Vocal Communication, and Cerebellar Circuit Connectivity in the TcMAC21 Mouse.Research square · 2025Article
- Synaptic inhibitory dynamics drive benzodiazepine response in pediatric status epilepticus.Epilepsia · 2025Article
- A Dive Into Cerebellar Dysfunction, Motor Deficits and GABAergic Signaling in Down Syndrome.Cureus · 2025Review
- Sevoflurane-induced overexpression of extrasynaptic α5-GABAAging cell · 2024Article
- The role of Down syndrome cell adhesion molecule in Down syndrome.Medical review (2021) · 2024Review
- Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?Frontiers in cellular neuroscience · 2024Article
- Understanding the genetic mechanisms and cognitive impairments in Down syndrome: towards a holistic approach.Journal of neurology · 2024Review
- The molecular basis of drug selectivity for α5 subunit-containing GABANature structural & molecular biology · 2023Article
- Long-term α5 GABA A receptor negative allosteric modulator treatment reduces NMDAR-mediated neuronal excitation and maintains basal neuronal inhibition.Neuropharmacology · 2023Article
- Synthesis and Receptor Binding Studies of α5 GABAMolecules (Basel, Switzerland) · 2023Article
- Shared Mechanisms of GABAergic and Opioidergic Transmission Regulate Corticolimbic Reward Systems and Cognitive Aspects of Motivational Behaviors.Brain sciences · 2023Review
- Control of contextual memory through interneuronal α5-GABAPNAS nexus · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Down syndrome (DS) is associated with neurological complications, including cognitive deficits that lead to impairment in intellectual functioning. Increased GABA-mediated inhibition has been proposed as a mechanism underlying deficient cognition in the Ts65Dn (TS) mouse model of DS. We show that chronic treatment of these mice with RO4938581 (3-bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine), a selective GABA(A) α5 negative allosteric modulator (NAM), rescued their deficits in spatial learning and memory, hippocampal synaptic plasticity, and adult neurogenesis. We also show that RO4938581 normalized the high density of GABAergic synapse markers in the molecular layer of the hippocampus of TS mice. In addition, RO4938581 treatment suppressed the hyperactivity observed in TS mice without inducing anxiety or altering their motor abilities. These data demonstrate that reducing GABAergic inhibition with RO4938581 can reverse functional and neuromorphological deficits of TS mice by facilitating brain plasticity and support the potential therapeutic use of selective GABA(A) α5 NAMs to treat cognitive dysfunction in DS.
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Registered trials
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.