Copper-uptake is critical for the down regulation of synapsin and dynamin induced by neocuproine: Modulation of synaptic activity in hippocampal neurons

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dc.contributor.authorCastro, Patricio A.
dc.contributor.authorRamirez, Alejandra
dc.contributor.authorSepúlveda, Fernando J.
dc.contributor.authorPeters, Christian
dc.contributor.authorFierro, Humberto
dc.contributor.authorWaldron, Javier
dc.contributor.authorLuza, Sandra
dc.contributor.authorFuentealba, Jorge
dc.contributor.authorMuñoz, Francisco J.
dc.contributor.authorDe Ferrari, Giancarlo V.
dc.contributor.authorBush, Ashley I.
dc.contributor.authorAguayo, Luis G.
dc.contributor.authorOpazo, Carlos
dc.date.accessioned2023-07-13T20:43:27Z
dc.date.available2023-07-13T20:43:27Z
dc.date.issued2014
dc.descriptionIndexación: Scopus.es
dc.description.abstractExtracellular 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.es
dc.description.urihttps://www.frontiersin.org/articles/10.3389/fnagi.2014.00319/full
dc.identifier.citationFrontiers in Aging Neuroscience. Volume 6, Issue OCT. 2014 Article number 319es
dc.identifier.doiDOI: 10.3389/fnagi.2014.00319
dc.identifier.issn1663-4365
dc.identifier.urihttps://repositorio.unab.cl/xmlui/handle/ria/51659
dc.language.isoenes
dc.publisherFrontiers Research Foundationes
dc.rights.licenseAtribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.es
dc.subjectCopperes
dc.subjectZinces
dc.subjectNeocuproinees
dc.subjectSynaptic Activityes
dc.subjectDynamin,es
dc.subjectSynapsines
dc.subjectHyperexcitabilityes
dc.subjectEpileptiform-Like Activityes
dc.titleCopper-uptake is critical for the down regulation of synapsin and dynamin induced by neocuproine: Modulation of synaptic activity in hippocampal neuronses
dc.typeArtículoes
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