title: Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system.
abstract: Metformin is a widely used oral antidiabetic drug with known anti-inflammatory properties due to its action on AMPK protein. This drug has shown a protective effect on various tissues, including cortical neurons. The aim of this study was to determine the effect of metformin on the dopaminergic neurons of the substantia nigra of mice using the animal model of Parkinson's disease based on the injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an inhibitor of the mitochondrial complex I. In vivo and in vitro experiments were used to study the activation of microglia and the damage of the dopaminergic neurons. Our results show that metformin reduced microglial activation measured both at cellular and molecular levels. Rather than protecting, metformin exacerbated dopaminergic damage in response to MPTP. Our data suggest that, contrary to other brain structures, metformin treatment could be deleterious for the dopaminergic system. Hence, metformin treatment may be considered as a risk factor for the development of Parkinson's disease.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Afrah A K
authors.initials: AA
authors.lastname: Ismaiel
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Espinosa-Oliva
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Martiniano
authors.initials: M
authors.lastname: Santiago
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: García-Quintanilla
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Oliva-Martín
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Herrera
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Venero
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain. Electronic address: depablos@us.es.
authors.forename: Rocío M
authors.initials: RM
authors.lastname: de Pablos
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D018929:Cell Culture Techniques; D002460:Cell Line; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D017382:Reactive Oxygen Species; D008687:Metformin; D004298:Dopamine
keywords: Diabetes mellitus; Dopaminergic system; MPTP; Metformin; Parkinson's disease