Metformin, besides exhibiting strong in vivo anti-inflammatory properties, increases mptp-induced damage to the nigrostriatal dopaminergic system
| Autor: | Ana M. Espinosa-Oliva, Albert García-Quintanilla, Afrah Abdul Ismaiel, José L. Venero, Rocío M. de Pablos, Maria Jose Oliva-Martin, Antonio J. Herrera, Martiniano Santiago |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Parkinson's disease endocrine system diseases Dopamine Anti-Inflammatory Agents Cell Culture Techniques Substantia nigra PINK1 Apoptosis Pharmacology Biology Toxicology Real-Time Polymerase Chain Reaction Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Parkinsonian Disorders In vivo Internal medicine medicine Animals MPTP Dopaminergic Neurons Dopaminergic nutritional and metabolic diseases AMPK medicine.disease Immunohistochemistry Corpus Striatum Metformin Mice Inbred C57BL Substantia Nigra Oxidative Stress 030104 developmental biology Endocrinology nervous system chemistry Microglia Reactive Oxygen Species 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Toxicology and applied pharmacology. 298 |
| ISSN: | 1096-0333 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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