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Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease

 

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dc.creator Tayara, Khadija es
dc.creator Espinosa Oliva, Ana María es
dc.creator García Domínguez, Irene es
dc.creator Ismaiel, Afrah Abdul es
dc.creator Boza Serrano, Antonio es
dc.creator Deierborg, Tomas es
dc.creator Martínez de Pablos, Rocío es
dc.creator Machado de la Quintana, Alberto es
dc.creator Herrera Carmona, Antonio José es
dc.creator Venero Recio, José Luis es
dc.date.accessioned 2018-12-13T13:16:35Z
dc.date.available 2018-12-13T13:16:35Z
dc.date.issued 2018
dc.identifier.citation Tayara, K., Espinosa Oliva, A.M., García Domínguez, I., Ismaiel, A.A., Boza Serrano, A., Deierborg, T.,...,Venero Recio, J.L. (2018). Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease. Frontiers in Cellular Neuroscience, 12 (440), 1-16.
dc.identifier.issn 1662-5102 es
dc.identifier.uri https://hdl.handle.net/11441/80975
dc.description.abstract The oral antidiabetic drug metformin is known to exhibit anti-inflammatory properties through activation of AMP kinase, thus protecting various brain tissues as cortical neurons, for example. However, the effect of metformin on the substantia nigra (SN), the main structure affected in Parkinson’s disease (PD), has not yet been studied in depth. Inflammation is a key feature of PD and it may play a central role in the neurodegeneration that takes place in this disorder. The aim of this work was to determine the effect of metformin on the microglial activation of the SN of rats using the animal model of PD based on the injection of the pro-inflammogen lipopolysaccharide (LPS). In vivo and in vitro experiments were conducted to study the activation of microglia at both the cellular and molecular levels. Our results indicate that metformin overall inhibits microglia activation measured by OX-6 (MHCII marker), IKKβ (pro-inflammatory marker) and arginase (anti-inflammatory marker) immunoreactivity. In addition, qPCR experiments reveal that metformin treatment minimizes the expression levels of several pro- and anti-inflammatory cytokines. Mechanistically, the drug decreases the phosphorylated forms of mitogen-activated protein kinases (MAPKs) as well as ROS generation through the inhibition of the NADPH oxidase enzyme. However, metformin treatment fails to protect the dopaminergic neurons of SN in response to intranigral LPS. These findings suggest that metformin could have both beneficial and harmful pharmacological effects and raise the question about the potential use of metformin for the prevention and treatment of PD. es
dc.description.sponsorship España MINECO SAF2015-64171-R es
dc.format application/pdf es
dc.language.iso eng es
dc.publisher Frontiers Media es
dc.relation.ispartof Frontiers in Cellular Neuroscience, 12 (440), 1-16.
dc.rights Attribution-NonCommercial-NoDerivatives 4.0 Internacional *
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ *
dc.subject neuroinflammation es
dc.subject Parkinson’s disease es
dc.subject metformin es
dc.subject microglia activation es
dc.subject animal model es
dc.subject AMPK es
dc.title Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease es
dc.type info:eu-repo/semantics/article es
dc.type.version info:eu-repo/semantics/publishedVersion es
dc.rights.accessrights info:eu-repo/semantics/openAccess es
dc.contributor.affiliation Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular es
dc.relation.projectID SAF2015-64171-R es
dc.relation.publisherversion http://dx.doi.org/10.3389/fncel.2018.00440 es
dc.identifier.doi 10.3389/fncel.2018.00440 es
idus.format.extent 16 p. es
dc.journaltitle Frontiers in Cellular Neuroscience es
dc.publication.volumen 12 es
dc.publication.issue 440 es
dc.publication.initialPage 1 es
dc.publication.endPage 16 es
dc.contributor.funder Ministerio de Economía y Competitividad (MINECO). España
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