Bee Venom-Derived BBB Shuttle and its Correlation with Oligodendrocyte Proliferation Markers in Mice Model of Multiple Sclerosis.
Tannaz Danesh-SetaFatemeh EmamiMohammad Hossein Nasr-EsfahaniKamran GhaediMehdi AliomraniPublished in: Neurotoxicity research (2021)
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.
Keyphrases
- multiple sclerosis
- blood brain barrier
- induced apoptosis
- signaling pathway
- phase ii
- white matter
- high fat diet induced
- cell cycle arrest
- clinical trial
- diabetic rats
- high glucose
- drug induced
- cell death
- spinal cord injury
- open label
- oxidative stress
- endoplasmic reticulum stress
- cerebral ischemia
- skeletal muscle
- combination therapy
- climate change
- insulin resistance
- metabolic syndrome
- angiotensin ii
- wild type
- optical coherence tomography
- preterm birth