Open AccessMelatonin antagonizes interleukin‐18‐mediated inhibition on neural stem cell proliferation and differentiation
Author(s) -
Li Zheng,
Li Xingye,
Chan Matthew T.V.,
Wu William Ka Kei,
Tan DunXian,
Shen Jianxiong
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13140
Subject(s) - melatonin , glial cell line derived neurotrophic factor , neurosphere , neural stem cell , neurotrophic factors , neurotrophin , biology , microbiology and biotechnology , stem cell , cell growth , cellular differentiation , pharmacology , medicine , endocrinology , adult stem cell , biochemistry , receptor , gene
Neural stem cells ( NSC s) 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 NSC s and IL ‐18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL ‐18 on NSC s 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 NSC s. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSC s. 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 NSC s in neuroinflammatory diseases.