Human neural precursor cells express functional kappa-opioid receptors.
Wen S Sheng1, Shuxian Hu, Greg Herr
1The Center for Infectious Diseases and Microbiology Translational Research, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. sheng008@umn.edu
Summary
Activation of kappa-opioid receptors (KORs) stimulates human neural precursor cell (NPC) proliferation and migration, crucial for brain development and repair. These findings highlight KORs as potential targets for neurological therapies.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Pharmacology
Background:
- Neural stem cells (NSCs) and neural precursor cells (NPCs) are vital for brain development and repair, exhibiting migration toward injury sites.
- Cellular and environmental factors influence NPC proliferation and migration.
- Previous studies reported opioid receptor expression in various stem and progenitor cells.
Purpose of the Study:
- To investigate the expression and functional role of kappa-opioid receptors (KORs) in human fetal brain-derived NPCs.
- To determine if KOR activation affects NPC proliferation and migration.
Main Methods:
- Enrichment of human fetal brain-derived NPCs (>90% nestin-positive).
- Treatment with KOR ligands (dynorphin(1-17), U50,488) and a selective KOR antagonist (nor-binaltorphimine).
- Assessment of NPC proliferation and migration rates.
- Evaluation of KOR mRNA expression following retinoic acid treatment.
Main Results:
- Robust expression of KORs was confirmed in human NPCs.
- KOR agonists (dynorphin(1-17), U50,488) dose-dependently stimulated NPC proliferation and migration.
- A KOR antagonist partially inhibited these effects, indicating KOR involvement.
- Retinoic acid treatment suppressed KOR mRNA expression.
Conclusions:
- Activation of kappa-opioid receptors significantly impacts human neural precursor cell proliferation and migration.
- These findings suggest KORs play a role in human brain development and repair processes.
- KORs represent a potential therapeutic target for neurological conditions requiring neural repair.
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