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A study on the effect of JNJ-10397049 on proliferation and differentiation of neural precursor cells

  • Neda Karami (Division of Medical Biotechnology, Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences) ;
  • Hassan Azari (Neural Stem Cell Laboratory, Department of Neurosurgery, McKnight Brain Institute, University of Florida) ;
  • Moosa Rahimi (Laboratory of Basic Sciences, Mohammad Rasul Allah Research Tower, Shiraz University of Medical Sciences) ;
  • Hadi Aligholi (Department of Neuroscience, School of Advanced Medical Sciences and Technology, Shiraz University of Medical Sciences) ;
  • Tahereh Kalantari (Division of Medical Biotechnology, Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences)
  • Received : 2021.10.03
  • Accepted : 2021.12.27
  • Published : 2022.06.30

Abstract

The orexin 2 receptor plays a central role in maintaining sleep and wakefulness. Recently, it has been shown that sleep and wakefulness orchestrate the proliferation and differentiation of oligodendrocytes. Here, we explored the role of a selective orexin 2 receptor antagonist (JNJ-10397049) in proliferation and differentiation of neural progenitor cells (NPCs). We evaluated the proliferation potential of NPCs after exposure to different concentrations of JNJ-10397049 by using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide and neurosphere assays. Moreover, the expression of differentiation markers was assessed by immunocytochemistry and real-time polymerase chain reaction. JNJ-10397049 significantly increased the proliferation of NPCs at lower concentrations. In addition, orexin 2 receptor antagonist facilitated progression of differentiation of NPCs towards oligodendroglial lineage by considerable expression of Olig2 and 2',3'-cyclicnucleotide 3'-phosphodiesterase as well as decreased expression of nestin marker. The results open a new avenue for future investigations in which the production of more oligodendrocytes from NPCs is needed.

Keywords

Acknowledgement

This work was financially supported by a grant number 14482 from Shiraz University of Medical Sciences, Shiraz, Iran. We are grateful to Zahra Zeraatpisheh and Marjan Ghorbanpour for their technical help and support. We had collaboration with Department of Neuroscience, School of Advanced Medical Sciences and Technology for performing this research.

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