期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 298, 期 -, 页码 19-30出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2016.03.004
关键词
Parkinson's disease; Metformin; Diabetes mellitus; MPTP; Dopaminergic system
资金
- Junta de Andalucia [P09-CTS-5244, P10-CTS-6494]
- Spanish Ministerio de Economia y Competitividad [SAF2012-3902]
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. (C) 2016 Elsevier Inc. All rights reserved.
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