Evaluating the Effect of Metformin on the Expression Levels of Sirt1, Nlrp3 and Il18 in the Brain of Cuprizone-Induced Demyelination Mice Model; [ردزغمیاهشوملدم وil18 Nlrp3 یسرربریثأتنیمروفتمربحطسنایب،Sirt1 نویسانیلیمدءاقلاهدشابنوزیرپوک]



Abdi M ; Kashani IR ; Shabani M ; Hajiallahverdipoor K ; Daneshi E ; Abouzaripour M ; Pasbakhsh P
Source: Scientific Journal of Kurdistan University of Medical Sciences Published:2025

Abstract

Background and Aim: Multiple Sclerosis (MS) is a degenerative disease of the central nervous system characterized by the presence of demyelinating plaques and inflammation. The Nlrp3 inflammasome has been shown to be activated in MS and contributes to its progression. Metformin is a blood sugar-lowering drug with anti-inflammatory property. Given the importance of inflammation in the pathogenesis of MS, the current study aimed to evaluate the effect of metformin administration on the Nlrp3 inflammasome activity in a cuprizone-induced demyelination model. Materials and Methods: In this study, male C57BL/6 mice were randomly distributed to the following groups: 1) control group that received a normal diet with intraperitoneal injection of normal saline, 2) cuprizone (CPZ) group which received ground food containing 0.2% cuprizone for 3 or 5 weeks, 3) treatment group that received a CPZ diet with intraperitoneal injection of metformin (100 mg/kg) for 3 or 5 weeks. Real-Time PCR technique was used to evaluate the expression levels of N3 and Sirt1 genes in the corpus callosum. Nlrp3 and IL18 protein levels were measured using immunohistochemistry (IHC) Results: RT-PCR results showed that cuprizone significantly increased the mRNA and protein levels of Nlrp3 compared to the control group. However, metformin administration decreased Nlrp3 at the gene and protein levels compared to the CPZ groups. Also, metformin decreased the protein levels of IL18 compared to the CPZ groups. In addition, CPZ increased the expression of Sirt1 gene compared to the control group, while metformin therapy had no effect on Sirt1 expression. Conclusion: Taken together, our findings indicate that metformin, by suppressing Nlrp3 inflammosome, has promising effects in modulating inflammatory responses in the cuprizone-induced demyelination model. © 2018 the Author (s).