ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Glutamatergic transmission aberration: a major cause of behavioral deficits in a murine model of Down's syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 63 citations in OpenAlex.
- Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration.Nature communications · 2022Trial
- Prenatal Metabolomics Analysis and Fetal Congenital Anomalies and Genetic Conditions: A Review of Current Literature.Prenatal diagnosis · 2025Review
- Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Alzheimer's Disease-Related Endosomal and Synaptic Dysfunction with Cholinergic Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025Review
- A Dive Into Cerebellar Dysfunction, Motor Deficits and GABAergic Signaling in Down Syndrome.Cureus · 2025Review
- Current insights and prospects for the pathogenesis and treatment of clinical manifestations associated with Down syndrome through neurotransmitter, inflammatory, and oxidative stress pathways.Frontiers in pharmacology · 2025Review
- Neurodevelopmental Abnormalities in Down Syndrome: Assessing Structural and Functional Deficits.Cureus · 2024Review
- Mitovesicles secreted into the extracellular space of brains with mitochondrial dysfunction impair synaptic plasticity.Molecular neurodegeneration · 2024Article
- Hippocampal CA1 Pyramidal Neurons Display Sublayer and Circuitry Dependent Degenerative Expression Profiles in Aged Female Down Syndrome Mice.Journal of Alzheimer's disease : JAD · 2024Article
- 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
- Maternal choline supplementation protects against age-associated cholinergic and GABAergic basal forebrain neuron degeneration in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.Neurobiology of disease · 2023Article
- Basal forebrain cholinergic neurons are vulnerable in a mouse model of Down syndrome and their molecular fingerprint is rescued by maternal choline supplementation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Neuronal SNAP-23 is critical for synaptic plasticity and spatial memory independently of NMDA receptor regulation.iScience · 2023Article
- Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer's Disease.Molecular neurobiology · 2021Article
- Role of DSCAM in the Development of Neural Control of Movement and Locomotion.International journal of molecular sciences · 2021Review
- Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome.PloS one · 2020Article
- A pleiotropic role for exosomes loaded with the amyloid β precursor protein carboxyl-terminal fragments in the brain of Down syndrome patients.Neurobiology of aging · 2019Article
- Lysosomal Dysfunction in Down Syndrome Is APP-Dependent and Mediated by APP-βCTF (C99).The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Trisomy 21, or Down's syndrome (DS), is the most common genetic cause of intellectual disability. Altered neurotransmission in the brains of DS patients leads to hippocampus-dependent learning and memory deficiency. Although genetic mouse models have provided important insights into the genes and mechanisms responsible for DS-specific changes, the molecular mechanisms leading to memory deficits are not clear. We investigated whether the segmental trisomy model of DS, Ts[Rb(12.1716)]2Cje (Ts2), exhibits hippocampal glutamatergic transmission abnormalities and whether these alterations cause behavioral deficits. Behavioral assays demonstrated that Ts2 mice display a deficit in nest building behavior, a measure of hippocampus-dependent nonlearned behavior, as well as dysfunctional hippocampus-dependent spatial memory tested in the object-placement and the Y-maze spontaneous alternation tasks. Magnetic resonance spectra measured in the hippocampi revealed a significantly lower glutamate concentration in Ts2 as compared with normal disomic (2N) littermates. The glutamate deficit accompanied hippocampal NMDA receptor1 (NMDA-R1) mRNA and protein expression level downregulation in Ts2 compared with 2N mice. In concert with these alterations, paired-pulse analyses suggested enhanced synaptic inhibition and/or lack of facilitation in the dentate gyrus of Ts2 compared with 2N mice. Ts2 mice also exhibited disrupted synaptic plasticity in slice recordings of the hippocampal CA1 region. Collectively, these findings imply that deficits in glutamate and NMDA-R1 may be responsible for impairments in synaptic plasticity in the hippocampus associated with behavioral dysfunctions in Ts2 mice. Thus, these findings suggest that glutamatergic deficits have a significant role in causing intellectual disabilities in DS.
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Registered trials
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