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Apamin administration impact on miR-219 and miR-155-3p expression in cuprizone induced multiple sclerosis model
Samira Gholami1, Mina Mirian2, Seyed Mehdi Eftekhari3
1School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran.
Abstract:
Multiple sclerosis (MS) is a chronic debilitating disease that attacks the central nervous system. This study aims to investigate miR-219 and miR-155-3p expression levels involved in the myelination process following the administration of apamin peptide in the model of multiple sclerosis disease. Forty-four 8 week C57BL/6 male mice (22 ± 5 g) randomly divided into six groups. Apamin (100 µg/kg/BW) was administered intraperitoneally as a co-treatment during phase I (demyelination) or post-treatment phase II (remyelination) twice a week in cuprizone induced MS model. At the end of study myelin content and microRNA expression levels were measured with LFB staining and quantitative Real-Time PCR method, respectively. It was observed that the intended microRNAs were dysregulated during the different phases of disease induction. After 6 weeks of cuprizone exposure, miR-219 downregulated in phase I in comparison with the negative control. On the other hand, the apamin co-treatment significantly inhibit the miR-155-3p upregulation during the phase I as compared with the cuprizone group (p < 0.0001). Apamin has more impact on the miR155-3p reduction in phase I than miR-219 elevation in phase II. It could be considered as a therapeutic option for decreasing plaque formation during the exacerbation phase of the MS disease. Apamin has more impact on the miR155-3p reduction in phase I than miR-219 elevation in phase II. It could be considered as a therapeutic option for decreasing plaque formation during the exacerbation phase of the MS disease.
Insights
Apamin peptide may reduce multiple sclerosis (MS) plaque formation by modulating miR-155-3p during demyelination. This offers a potential therapeutic strategy for MS exacerbations.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Multiple sclerosis (MS) is a chronic central nervous system disease impacting myelination.
- MicroRNAs (miRNAs) like miR-219 and miR-155-3p are implicated in MS pathogenesis.
- Apamin, a peptide toxin, is being investigated for its therapeutic potential in MS.
Purpose of the Study:
- To investigate the role of miR-219 and miR-155-3p in the myelination process of an MS model.
- To evaluate the effect of apamin peptide administration on miRNA expression and myelination in MS.
Main Methods:
- A cuprizone-induced mouse model of multiple sclerosis was utilized.
- Apamin peptide was administered during demyelination (phase I) or remyelination (phase II) phases.
- Myelin content was assessed using Luxol Fast Blue (LFB) staining, and microRNA levels were quantified via Real-Time PCR.
Main Results:
- miR-219 was downregulated in phase I (demyelination) compared to controls.
- Apamin co-treatment significantly inhibited miR-155-3p upregulation during phase I.
- Apamin demonstrated a greater effect on reducing miR-155-3p in phase I than on miR-219 in phase II.
Conclusions:
- Dysregulation of miR-219 and miR-155-3p occurs during different phases of MS.
- Apamin peptide shows therapeutic potential in mitigating MS plaque formation, particularly during the exacerbation phase.
- Modulation of miR-155-3p by apamin suggests a novel therapeutic avenue for MS treatment.
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