| Abstract No.: | A-C1093 |
| Country: | Canada |
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| Title: | LPS AND MPP+ -INDUCED INFLAMMATION IS MODULATED BY RESVERATROL AND QUERCETIN, TWO NATURAL POLYPHENOLS. |
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| Authors/Affiliations: | 1 Marilyn Plouffe*; 1 Geneviève Bureau; 1 Maria-Grazia Martinoli;
1 Université du Québec à Trois-Rivières, QC, Canada
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| Content: | Parkinson’s disease (PD) is a movement disorder that is characterized by a progressive loss of nigrostriatal dopaminergic neurons. Apoptotic death of these neurons may be initiated by oxidative stress and neuroinflammation. Indeed, microglial activation and subsequent production of cytokines have been proposed as mediators of neuroinflammation seen in PD. Moreover, recent evidences demonstrate that inhibition of oxidative stress and neuroinflammation can, in part, prevent degeneration of dopaminergic neurons. We have already show that two phytoestrogens, resveratrol and quercetin, are potent antioxidant molecules. The aim of our study was to investigate the anti-inflammatory potentials of these two phytoestrogens, on several parameters of neuroinflammation.
We have verified the effect of resveratrol and quercetin against lipopolysaccharide (LPS)-induced inflammation on N9 microglial cells. We also determined the potential of 1-methyl-4-phenypyridinium (MPP+), one of the most commun toxin used to induce PD in vitro, to stimulate neuroinflammation on N9 microglial cells. The level of inflammation was inferred by measuring gene transcription of several pro-inflammatory cytokines such as IL-1α and β, TNF-α and β, and IL-6, by RT-PCR. Then, N9 microglial cells-PC12 neuronal cells co-culture was used to examinate the effect of resveratrol and quercetin on dopaminergic neuronal cell death evoked by LPS-activated microglia. We also detected the apoptotic death by the TUNEL technique.
Pre-treatments of microglial cells with resveratrol or quercetin decreased the levels of expression of IL-1α and TNF-α mRNA induced by LPS. We have also demonstrated, in co-cultures of PC12 and N9 cells, that LPS-activated microglial cells may induce apoptotic death of neuronal PC12 cells. Then, treatment of N9 cells with LPS and resveratrol or quercetin could reduce inflammation by lowering IL-1α and TNF-α mRNA and, at the same time, decreased the apoptotic death of PC12 cells. In addition, the level of gene transcription of cytokines IL-6 and TNF-β was increased in MPP+-induced activation of N9 microglial cells.
Our results demonstrate that resveratrol or quercetin may reduce apoptotic death of neuronal cells induced by microglial activation, and suggest that these two phytoestrogens may be potent anti-inflammatory compounds. Furthermore, the parkinsonian toxin MPP+ may act as an effective inflammatory molecule and as such induce oxydative stress by modulatory cytokines expression.
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