ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic and memory deficits of Alzheimer's disease?
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers, 1 of them a synthesis that pooled it.
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Who cites it
164 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic Variations as Modifying Factors to Dietary Zinc Requirements-A Systematic Review.Nutrients · 2017Pooled it
- The role of zinc homeostasis in major depressive disorder: heterogeneous pathological mechanisms and therapeutic implications.Annals of medicine · 2026Review
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Zinc homeostasis imbalance: Potential therapeutic value in neurodegenerative diseases.Neural regeneration research · 2026Article
- Zinc and Copper Metallic Instability: Investigating Altered Metal Functionality in both Human and Animal Studies.Biological trace element research · 2026Review
- The Impact of Zinc on Cellular Dynamics, Brain Function, and its Therapeutic Potential in Neuronal Regeneration.Molecular neurobiology · 2026Review
- Imaging zinc speciation in the mouse hippocampus with µXANES Spectroscopic mapping.Metallomics : integrated biometal science · 2026Article
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- Dual Inhibitors of Acetylcholinesterase and Monoamine Oxidase-B for the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2025Review
- Zinc deficiency as possible link between immunosenescence and age-related diseases.Immunity & ageing : I & A · 2025Review
- The Astrocytic Zinc Transporter ZIP12 Is a Synaptic Protein That Contributes to Synaptic Zinc Levels in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- Structural insights into human zinc transporter ZnT1 mediated ZnEMBO reports · 2024Article
- Cell-type-specific enhancement of deviance detection by synaptic zinc in the mouse auditory cortex.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Interactive effect of air pollution and genetic risk of depression on processing speed by resting-state functional connectivity of occipitoparietal network.BMC medicine · 2024Article
- Metal Toxicity and Dementia Including Frontotemporal Dementia: Current State of Knowledge.Antioxidants (Basel, Switzerland) · 2024Review
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- Trans-synaptic Association of Vesicular Zinc Transporter 3 and Shank3 Supports Synapse-Specific Dendritic Spine Structure and Function in the Mouse Auditory Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
104 more citing papers are in PubMed but not listed here.
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Zinc transporter-3 (ZnT3) protein controls synaptic vesicular Zn(2+) levels, which is predicted to regulate normal cognitive function. Surprisingly, previous studies found that 6- to 10-week-old ZnT3 knock-out (KO) mice did not show impairment in the Morris water maze. We hypothesized that older ZnT3 KO animals would display a cognitive phenotype. Here, we report that ZnT3 KO mice exhibit age-dependent deficits in learning and memory that are manifest at 6 months but not at 3 months of age. These deficits are associated with significant alterations in key hippocampal proteins involved in learning and memory, as assessed by Western blot. These include decreased levels of the presynaptic protein SNAP25 (-46%; p < 0.01); the postsynaptic protein PSD95 (-37%; p < 0.01); the glutamate receptors AMPAR (-34%; p < 0.01), NMDAR2a (-64%; p < 0.001), and NMDAR2b (-49%; p < 0.05); the surrogate marker of neurogenesis doublecortin (-31%; p < 0.001); and elements of the BDNF pathway, pro-BDNF (-30%; p < 0.05) and TrkB (-22%; p < 0.01). In addition, there is a concomitant decrease in neuronal spine density (-6%; p < 0.05). We also found that cortical ZnT3 levels fall with age in wild-type mice (-50%; p < 0.01) in healthy older humans (ages, 48-91 years; r(2) = 0.47; p = 0.00019) and particularly in Alzheimer's disease (AD) (-36%; p < 0.0001). Thus, age-dependent loss of transsynaptic Zn(2+) movement leads to cognitive loss, and since extracellular beta-amyloid is aggregated by and traps this pool of Zn(2+), the genetic ablation of ZnT3 may represent a phenocopy for the synaptic and memory deficits of AD.
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