Divergent Effects of Metformin on an Inflammatory Model of Parkinson's Disease
| Autor: | Rocío M. de Pablos, Alberto Machado, Khadija Tayara, Antonio Boza-Serrano, Ana M. Espinosa-Oliva, Antonio J. Herrera, Afrah Abdul Ismaiel, José L. Venero, Tomas Deierborg, Irene García-Domínguez |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Educación, Cultura y Deporte (España), Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular, Ministerio de Economía y Competitividad (MINECO). España |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
AMPK microglia activation Inflammation Substantia nigra Pharmacology lcsh:RC321-571 neuroinflammation 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Neuroinflammation medicine lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Microglia activation NADPH oxidase Microglia biology Chemistry Kinase animal model Neurodegeneration medicine.disease Metformin Animal models 030104 developmental biology medicine.anatomical_structure biology.protein Parkinson’s disease medicine.symptom metformin 030217 neurology & neurosurgery Neuroscience medicine.drug |
| Zdroj: | idUS. Depósito de Investigación de la Universidad de Sevilla instname Frontiers in Cellular Neuroscience, Vol 12 (2018) Digital.CSIC. Repositorio Institucional del CSIC Frontiers in Cellular Neuroscience |
| Popis: | 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. This work was supported by a grant from the Spanish Ministerio de Economia y Competitividad SAF2015-64171-R (MINECO/FEDER, EU). KT was supported by a studentship provided by Erasmus Mundus -Phoenix Programme. IG-D was supported by pre-doctoral fellowships from Spanish Ministerio de Educación, Cultura y Deporte. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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