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Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease
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 di...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258993/ https://www.ncbi.nlm.nih.gov/pubmed/30519161 http://dx.doi.org/10.3389/fncel.2018.00440 |
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author | Tayara, Khadija Espinosa-Oliva, Ana M. García-Domínguez, Irene Ismaiel, Afrah Abdul Boza-Serrano, Antonio Deierborg, Tomas Machado, Alberto Herrera, Antonio J. Venero, José L. de Pablos, Rocío M. |
author_facet | Tayara, Khadija Espinosa-Oliva, Ana M. García-Domínguez, Irene Ismaiel, Afrah Abdul Boza-Serrano, Antonio Deierborg, Tomas Machado, Alberto Herrera, Antonio J. Venero, José L. de Pablos, Rocío M. |
author_sort | Tayara, Khadija |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6258993 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62589932018-12-05 Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease Tayara, Khadija Espinosa-Oliva, Ana M. García-Domínguez, Irene Ismaiel, Afrah Abdul Boza-Serrano, Antonio Deierborg, Tomas Machado, Alberto Herrera, Antonio J. Venero, José L. de Pablos, Rocío M. Front Cell Neurosci Neuroscience 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. Frontiers Media S.A. 2018-11-21 /pmc/articles/PMC6258993/ /pubmed/30519161 http://dx.doi.org/10.3389/fncel.2018.00440 Text en Copyright © 2018 Tayara, Espinosa-Oliva, García-Domínguez, Ismaiel, Boza-Serrano, Deierborg, Machado, Herrera, Venero and de Pablos. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Tayara, Khadija Espinosa-Oliva, Ana M. García-Domínguez, Irene Ismaiel, Afrah Abdul Boza-Serrano, Antonio Deierborg, Tomas Machado, Alberto Herrera, Antonio J. Venero, José L. de Pablos, Rocío M. Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease |
title | Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease |
title_full | Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease |
title_fullStr | Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease |
title_full_unstemmed | Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease |
title_short | Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease |
title_sort | divergent effects of metformin on an inflammatory model of parkinson’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6258993/ https://www.ncbi.nlm.nih.gov/pubmed/30519161 http://dx.doi.org/10.3389/fncel.2018.00440 |
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