Journal
ANATOMY & CELL BIOLOGY
Volume 55, Issue 2, Pages 179-189Publisher
MEDRANG
DOI: 10.5115/acb.21.202
Keywords
Orexins; Orexin receptors; JNJ 10397049; Oligodendroglia; Neural stem cells
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Funding
- Shiraz University of Medical Sciences, Shiraz, Iran [14482]
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This study demonstrates that the selective orexin 2 receptor antagonist JNJ-10397049 can enhance the proliferation of neural progenitor cells (NPCs) and facilitate their differentiation towards the oligodendroglial lineage. These findings provide insights into the potential role of orexin 2 receptor antagonist in promoting oligodendrocyte production from NPCs.
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'-cyclic nucleotide 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.
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