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Published on: August 6, 2020
A study on the effect of JNJ-10397049 on proliferation and differentiation of neural precursor cells
Neda Karami1,2, Hassan Azari3, Moosa Rahimi4
1Division of Medical Biotechnology, Department of Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
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'-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.
Insights
Orexin 2 receptor antagonist JNJ-10397049 promotes neural progenitor cell (NPC) proliferation and enhances differentiation into oligodendrocytes. This finding offers new therapeutic avenues for conditions requiring oligodendrocyte regeneration.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- The orexin 2 receptor is crucial for regulating sleep-wake cycles.
- Sleep and wakefulness influence oligodendrocyte development.
- Neural progenitor cells (NPCs) are key to generating new oligodendrocytes.
Purpose of the Study:
- To investigate the effect of a selective orexin 2 receptor antagonist (JNJ-10397049) on NPC proliferation and differentiation.
- To explore the potential of targeting the orexin 2 receptor for oligodendrocyte production.
Main Methods:
- NPCs were treated with varying concentrations of JNJ-10397049.
- Proliferation was assessed using MTT and neurosphere assays.
- Differentiation markers (Olig2, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, nestin) were analyzed via immunocytochemistry and real-time PCR.
Main Results:
- JNJ-10397049 significantly increased NPC proliferation at lower concentrations.
- The antagonist promoted NPC differentiation towards the oligodendroglial lineage.
- Upregulation of Olig2 and 2',3'-cyclic-nucleotide 3'-phosphodiesterase and downregulation of nestin were observed.
Conclusions:
- Orexin 2 receptor antagonism by JNJ-10397049 promotes NPC proliferation and oligodendroglial differentiation.
- This suggests a novel strategy for enhancing oligodendrocyte production from NPCs.
- Further research is warranted to explore therapeutic applications.
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