ArticleNature medicine2015
Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed, 268 citations in OpenAlex.
- Trial
- Effects of Bumetanide on Neurocognitive Functioning in Children with Autism Spectrum Disorder: Secondary Analysis of a Randomized Placebo-Controlled Trial.Journal of autism and developmental disorders · 2024Trial
- Restoration of gamma-aminobutyric acid homeostasis: A novel approach to alleviating central nervous system injury-associated immunodepression syndrome.Neural regeneration research · 2026Article
- Learning Dynamics in Biophysical Spiking Network Models Are Shaped by KCC2/NKCC1 Cotransporter Stoichiometry.The European journal of neuroscience · 2026Article
- Infantile epileptic spasms syndrome: Mechanisms and therapeutic approaches.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Microglia drive synaptic and functional connectivity deficits in the Ts65Dn mouse model of Down syndrome by affecting inhibition.Acta neuropathologica communications · 2025Article
- Molecular cartography of the human down syndrome and trisomic mouse brain.Nature communications · 2025Article
- Chloride Homeostasis in Neuronal Disorders: Bridging Measurement to Therapy.Life (Basel, Switzerland) · 2025Review
- Emerging Insights into the Pathogenic Mechanisms of Dravet Syndrome.Neurochemical research · 2025Review
- Repurposing Caffeine, Metformin, and Furosemide to Target Schizophrenia-Related Impairments in a Triple-Hit Rat Model.International journal of molecular sciences · 2025Article
- Developmental dynamics of marmoset prefrontal cortical SST and PV interneuron networks highlight primate-specific features.Development (Cambridge, England) · 2025Article
- NKCC1 inhibition improves sleep quality and EEG information content in a Down syndrome mouse model.iScience · 2025Article
- Limitations of genomics to predict and treat autism: a disorder born in the womb.Journal of medical genetics · 2025Review
- The NKCC1 Inhibitor Bumetanide Restores Cortical Feedforward Inhibition and Lessens Sensory Hypersensitivity in Early Postnatal Fragile X Mice.Biological psychiatry · 2025Article
- Infantile Spasms in Pediatric Down Syndrome: Potential Mechanisms Driving Therapeutic Considerations.Children (Basel, Switzerland) · 2024Review
- Exploring crystallized and fluid intelligence in down syndrome using graph theory.Scientific reports · 2024Article
- Alterations in aperiodic and periodic EEG activity in young children with Down syndrome.Neurobiology of disease · 2024Article
- NgfrNature communications · 2024Article
- Developmental dynamics of the prefrontal cortical SST and PV interneuron networks: Insights from the monkey highlight human-specific features.bioRxiv : the preprint server for biology · 2024Article
- Heterogeneous subpopulations of GABAiScience · 2024Article
92 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Down syndrome (DS) is the most frequent genetic cause of intellectual disability, and altered GABAergic transmission through Cl(-)-permeable GABAA receptors (GABAARs) contributes considerably to learning and memory deficits in DS mouse models. However, the efficacy of GABAergic transmission has never been directly assessed in DS. Here GABAAR signaling was found to be excitatory rather than inhibitory, and the reversal potential for GABAAR-driven Cl(-) currents (ECl) was shifted toward more positive potentials in the hippocampi of adult DS mice. Accordingly, hippocampal expression of the cation Cl(-) cotransporter NKCC1 was increased in both trisomic mice and individuals with DS. Notably, NKCC1 inhibition by the FDA-approved drug bumetanide restored ECl, synaptic plasticity and hippocampus-dependent memory in adult DS mice. Our findings demonstrate that GABA is excitatory in adult DS mice and identify a new therapeutic approach for the potential rescue of cognitive disabilities in individuals with DS.
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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.