Melatonin attenuates dimethyl sulfoxide– and Zika virus–induced degeneration of porcine induced neural stem cells

Abstract

Domestic pigs have become increasingly popular as a model for human diseases such as neurological diseases. Drug discovery platforms have increasingly been used to identify novel compounds that combat neurodegeneration. Currently, bioactive molecules such as melatonin have been demonstrated to offer a neuroprotective effect in several studies. However, a neurodegenerative platform to study novel compounds in a porcine model has not been fully established. In this study, characterized porcine induced neural stem cells (iNSCs) were used for evaluation of the protective effect of melatonin against chemical and pathogenic stimulation. First, the effects of different concentrations of melatonin on the proliferation of porcine iNSCs were studied. Second, porcine iNSCs were treated with the appropriate concentration of melatonin prior to induced degeneration with dimethyl sulfoxide or Zika virus (ZIKV). The results demonstrated that the percentages of Ki67 expression in porcine iNSCs cultured in 0.1, 1, and 10 nM melatonin were not significantly different from that in the control groups. Melatonin at 1 nM protected porcine iNSCs from DMSO-induced degeneration, as confirmed by a dead cell exclusion assay and mitochondrial membrane potential (ΔΨm) analysis. In addition, pretreatment with melatonin reduced the percentage of dead porcine iNSCs after ZIKV infection. Melatonin increased the ΔΨm, resulting in a decrease in cell degeneration. However, pretreatment with melatonin was unable to suppress ZIKV replication in porcine iNSCs. In conclusion, the present study demonstrated the anti-degenerative effect of melatonin against DMSO-and ZIKV-induced degeneration in porcine iNSCs.

Assessing the antiviral potential of melatonin: A comprehensive systematic review

“…With the aid of a molecular docking technique, the authors also showed that melatonin had a high binding affinity to the nonstructural protein (NS3) of the virus; this may be a mechanism by which melatonin inhibits the Zika infection. The second report documented that melatonin reduced degeneration and death of porcine neural stem cells 23 . Since there is no specific treatment for a Zika infection, the information summarised here may be useful in reducing the severity of this disease.…”

“…The second report documented that melatonin reduced degeneration and death of porcine neural stem cells. 23 Since there is no specific treatment for a Zika infection, the information summarised here may be useful in reducing the severity of this disease.…”