RT Journal Article
T1 Divergent Effects of Metformin on an Inflammatory Model of Parkinson's Disease.
A1 Tayara, Khadija
A1 Espinosa-Oliva, Ana M
A1 Garcia-Dominguez, Irene
A1 Ismaiel, Afrah Abdul
A1 Boza-Serrano, Antonio
A1 Deierborg, Tomas
A1 Machado, Alberto
A1 Herrera, Antonio J
A1 Venero, Jose L
A1 de-Pablos, Rocio M
K1 AMPK
K1 Parkinson’s disease
K1 animal model
K1 metformin
K1 microglia activation
K1 neuroinflammation
AB 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.
PB Frontiers Research Foundation
SN 1662-5102
YR 2018
FD 2018-11-21
LK http://hdl.handle.net/10668/13284
UL http://hdl.handle.net/10668/13284
LA en
NO Tayara K, Espinosa-Oliva AM, García-Domínguez I, Ismaiel AA, Boza-Serrano A, Deierborg T, et al. Divergent Effects of Metformin on an Inflammatory Model of Parkinson's Disease. Front Cell Neurosci. 2018 Nov 21;12:440.
DS RISalud
RD Apr 7, 2025