Evaluation of apamin effects on myelination process in C57BL/6 mice model of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a demyelinating disease that causes chronic inflammation in the central nervous system. The aim of this study was to investigate the effects of apamin administration on myelination process. MS was induced by feeding cuprizone pellets (0.2) for 6 weeks (demyelination phase) followed by normal feeding for additional 2 weeks (remyelination phase). Briefly, C57BL/6 male mice were randomly divided into six groups. Group 1, received the regular food pellets. Group 2 contained two subgroups of 6 animals each (n = 2 x 6). First group received cuprizone for 6 weeks and the sacrificed while the second group after 6 weeks of cuprizone, received no treatment for additional 2 weeks. Group 3 (co-treatment group) was composed of two subgroups of 6 animals each (n = 2 x 6). Both subgroups received apamin (100 mu/kg) intraperitoneally twice a week for 6 weeks. First subgroup terminated at this time and the second subgroup was fed normal diet for two additional weeks. Group 4 (post-treatment, n = 6) received apamin (100 mu/kg) intraperitoneally twice a week for 2 weeks after cuprizone secession. Groups 5 and 6 (vehicle, n = 6 in each group) received phosphate buffered saline as the vehicle of apamin during demyelination and remyelination phase. At the end of each phase, mice were deeply anesthetized and perfused. Groups 5 and 6 (vehicle) received PBS as the vehicle during both phases. Mice were anesthetized, perfused with PBS through their heart, and their brains were removed. Brain sections stained with luxol fast blue and the images were analyzed. Apamin co-treatment significantly increased the myelin content as compared to the cuprizone group. Also, mild elevation in the myelinated areas was observed with apamin post-treatment in comparison with remyelination phase. Our results revealed that apamin prevents myelin destruction more significantly as compared to remyelination process. This observation explains the possible role of apamin in inhibiting the activation of the microglia cells than stimulation of the oligodendrocytic precursor cells.