Divergent effects of metformin on an inflammatory model of Parkinson’s disease

Research output: Contribution to journalArticle


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.


  • Khadija Tayara
  • Ana M. Espinosa-Oliva
  • Irene García-Domínguez
  • Afrah Abdul Ismaiel
  • Antonio Boza-Serrano
  • Tomas Deierborg
  • Alberto Machado
  • Antonio J. Herrera
  • José L. Venero
  • Rocío M. de Pablos
External organisations
  • University Hospital Virgen del Rocío
  • University of Seville
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • AMPK, Animal model, Metformin, Microglia activation, Neuroinflammation, Parkinson’s disease
Original languageEnglish
Article number440
JournalFrontiers in Cellular Neuroscience
Publication statusPublished - 2018 Nov 21
Publication categoryResearch