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Bee Venom–Derived BBB Shuttle and its Correlation with Oligodendrocyte Proliferation Markers in Mice Model of Multiple Sclerosis

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Abstract

Multiple sclerosis is a chronic demyelinating disease with a functional disturbance in the immune system and axonal damages. It was shown that Apamin as a blood–brain barrier shuttle acts as a Ca2+ activated K+ channels (SK channels) blocker. In this study, the effects of Apamin on oligodendrocyte differentiation markers were evaluated on an induced model of MS. Briefly, C57BL/6 male mice (22 ± 5 g) except the control group were fed with 0.2% (w/w) cuprizone pellets for 6 weeks. After cuprizone withdrawal, mice were divided randomly 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. Mice were anesthetized, perfused with phosphate-buffered saline, then fixed brains were coronally sectioned and the changes in oligodendrocytes markers such as Olig2, PDGFR-α, and BrdU incorporation were assessed by immunohistochemistry assay. Apamin administration increased Olig2+ cells in phase I as compared to the control group (p < 0.0001). Also, a decreasing trend in PDGFRa+ cells observed after cuprizone withdrawal (p < 0.001). 5-Bromo-2′-deoxyuridine (BrdU) incorporation test was confirmed stimulation of oligodendrocyte progenitor cell proliferation in phase I in the Apamin exposed group (p < 0.0001), especially at the subventricular zone. This study highlights the potential therapeutic effects of Apamin as a bee venom–derived peptide on oligodendrocyte precursor proliferation and elevation in myelin content in an oxidative induced multiple sclerosis model due to cuprizone exposure.

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Funding

This work was supported by the Iran National Science Foundation (INSF).

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Authors and Affiliations

  1. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

    Tannaz Danesh-Seta & Fatemeh Emami

  2. Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Mohammad Hossein Nasr-Esfahani

  3. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Kamran Ghaedi

  4. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Isfahan Pharmaceutical Science Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

    Mehdi Aliomrani

  5. Iranian National Science Foundation, Tehran, Iran

    Mehdi Aliomrani

Authors
  1. Tannaz Danesh-Seta
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  2. Fatemeh Emami
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  3. Mohammad Hossein Nasr-Esfahani
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  4. Kamran Ghaedi
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  5. Mehdi Aliomrani
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Correspondence to Mehdi Aliomrani.

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Danesh-Seta, T., Emami, F., Nasr-Esfahani, M.H. et al. Bee Venom–Derived BBB Shuttle and its Correlation with Oligodendrocyte Proliferation Markers in Mice Model of Multiple Sclerosis. Neurotox Res 39, 1181–1188 (2021). https://doi.org/10.1007/s12640-021-00361-x

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  • DOI: https://doi.org/10.1007/s12640-021-00361-x

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