Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell proliferation and differentiation

Zheng Li, Xingye Li, Matthew T.V. Chan, William Ka Kei Wu, Dun Xian Tan, Jianxiong Shen

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin treatment. Moreover, melatonin application increased the production of both brain-derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18-stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSCs. A potentially protective mechanism of melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The findings indicate that melatonin may play an important role promoting the survival of NSCs in neuroinflammatory diseases.

Original languageEnglish (US)
Pages (from-to)2163-2171
Number of pages9
JournalJournal of cellular and molecular medicine
Issue number9
StatePublished - Sep 2017
Externally publishedYes


  • interleukin-18
  • melatonin
  • neural stem cells
  • spinal cord injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology


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