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Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
Peroxisome proliferator-activated receptor γ ligands regulate neural stem cell proliferation and differentiation in
Jose A Morales-Garcia1, Rosario Luna-Medina, Clara Alfaro-Cervello
1Instituto de Investigaciones Biomédicas, CSIC-UAM, Arturo Duperier 4, 28029-Madrid, Spain.
Abstract:
Peroxisome proliferator-activated receptor gamma (PPARγ) belongs to a family of ligand-activated nuclear receptors and its ligands are known to control many physiological and pathological situations. Its role in the central nervous system has been under intense analysis during the last years. Here we show a novel function for PPARγ in controlling stem cell expansion in the adult mammalian brain. Adult rats treated with pioglitazone, a specific ligand of PPARγ, had elevated numbers of proliferating progenitor cells in the subventricular zone and the rostral migratory stream. Electron microscopy analysis also showed important changes in the subventricular zone ultrastructure of pioglitazone-treated animals including an increased number of migratory cell chains. These results were further confirmed in vitro. Neurosphere assays revealed significant increases in the number of neurosphere forming cells from pioglitazone- and rosiglitazone (two specific ligands of PPARγ receptor)-treated cultures that exhibited enhanced capacity for cell migration and differentiation. The effects of pioglitazone were blocked by the PPARγ receptor antagonists GW9662 and T0070907, suggesting that its effects are mediated by a mechanism dependent on PPARγ activation. These results indicate for the first time that activation of PPARγ receptor directly regulates proliferation, differentiation, and migration of neural stem cells in vivo.
Insights
Peroxisome proliferator-activated receptor gamma (PPARγ) activation enhances neural stem cell proliferation, migration, and differentiation in the adult brain. This discovery reveals a novel role for PPARγ in neurogenesis and brain repair mechanisms.
Area of Science:
- Neuroscience
- Stem Cell Biology
- Molecular Endocrinology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated nuclear receptor involved in numerous physiological and pathological processes.
- The function of PPARγ in the central nervous system is an area of active research.
- Previous studies have highlighted the involvement of PPARγ in various cellular functions, but its role in adult neurogenesis remained largely unexplored.
Purpose of the Study:
- To investigate the novel function of PPARγ in controlling neural stem cell expansion in the adult mammalian brain.
- To determine if PPARγ activation influences the proliferation, migration, and differentiation of neural stem cells.
- To elucidate the mechanism underlying PPARγ's effects on neural stem cells.
Main Methods:
- In vivo studies using adult rats treated with pioglitazone, a specific PPARγ ligand.
- Electron microscopy to analyze subventricular zone ultrastructure.
- In vitro neurosphere assays using primary neural stem cell cultures.
- Treatment with specific PPARγ ligands (pioglitazone, rosiglitazone) and antagonists (GW9662, T0070907).
Main Results:
- Pioglitazone treatment significantly increased proliferating progenitor cells in the subventricular zone and rostral migratory stream in vivo.
- Electron microscopy revealed enhanced migratory cell chains in the subventricular zone of treated animals.
- In vitro, PPARγ ligands increased neurosphere formation, cell migration, and differentiation capacity.
- The observed effects were blocked by PPARγ antagonists, confirming PPARγ-dependent mechanisms.
Conclusions:
- Activation of the PPARγ receptor directly regulates the proliferation, differentiation, and migration of neural stem cells in the adult mammalian brain.
- This study establishes a novel role for PPARγ in adult neurogenesis.
- PPARγ activation represents a potential therapeutic target for promoting neural repair and treating neurological disorders.
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