ArticleFrontiers in aging neuroscience2014
Copper-uptake is critical for the down regulation of synapsin and dynamin induced by neocuproine: modulation of synaptic activity in hippocampal neurons.
Article in Frontiers in aging neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
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- Inflammation in Metal-Induced Neurological Disorders and Neurodegenerative Diseases.Biological trace element research · 2024Review
- Enhanced small green fluorescent proteins as a multisensing platform for biosensor development.Frontiers in bioengineering and biotechnology · 2022Article
- Fluoxetine Induces Apoptotic and Oxidative Neuronal Death Associated with The Influx of Copper Ions in Cultured Neuronal Cells.Chonnam medical journal · 2020Article
- Anticancer response to disulfiram may be enhanced by co-treatment with MEK inhibitor or oxaliplatin: modulation by tetrathiomolybdate, KRAS/BRAF mutations and c-MYC/p53 status.Ecancermedicalscience · 2019Article
- CuChemical science · 2018Article
- Stabilization of Aliphatic Phosphines by Auxiliary Phosphine Sulfides Offers Zeptomolar Affinity and Unprecedented Selectivity for Probing Biological CuAngewandte Chemie (International ed. in English) · 2018Article
- Oxidative damage of copper chloride overload to the cultured rat astrocytes.American journal of translational research · 2016Article
- Editorial: Metals and neurodegeneration: restoring the balance.Frontiers in aging neuroscience · 2015Article
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13 authors at 5 institutions in 3 countries.
Funding
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Abstract
Extracellular and intracellular copper and zinc regulate synaptic activity and plasticity, which may impact brain functionality and human behavior. We have found that a metal coordinating molecule, Neocuproine, transiently increases free intracellular copper and zinc levels (i.e., min) in hippocampal neurons as monitored by Phen Green and FluoZin-3 fluorescence, respectively. The changes in free intracellular zinc induced by Neocuproine were abolished by the presence of a non-permeant copper chelator, Bathocuproine (BC), indicating that copper influx is needed for the action of Neocuproine on intracellular Zn levels. Moreover, Neocuproine decreased the mRNA levels of Synapsin and Dynamin, and did not affect the expression of Bassoon, tubulin or superoxide dismutase (SOD). Western blot analysis showed that protein levels of synapsin and dynamin were also down regulated in the presence of Neocuproine and that these changes were accompanied by a decrease in calcium transients and neuronal activity. Furthermore, Neocuproine decreased the number of active neurons, effect that was blocked by the presence of BC, indicating that copper influx is needed for the action of Neocuproine. We finally show that Neocuproine blocks the epileptiform-like activity induced by bicuculline in hippocampal neurons. Collectively, our data indicates that presynaptic protein configuration and function of primary hippocampal neurons is sensitive to transient changes in transition metal homeostasis. Therefore, small molecules able to coordinate transition metals and penetrate the blood-brain barrier might modify neurotransmission at the Central Nervous System (CNS). This might be useful to establish therapeutic approaches to control the neuronal hyperexcitabiltity observed in brain conditions that are associated to copper dyshomeotasis such as Alzheimer's and Menkes diseases. Our work also opens a new avenue to find novel and effective antiepilepsy drugs based in metal coordinating molecules.
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