1. Histone deacetylase inhibitors increase neuronal differentiation in adult forebrain precursor cells.
- Author
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Siebzehnrubl FA, Buslei R, Eyupoglu IY, Seufert S, Hahnen E, and Blumcke I
- Subjects
- Age Factors, Animals, Animals, Newborn, Basic Helix-Loop-Helix Transcription Factors genetics, Biomarkers metabolism, Cell Differentiation drug effects, Cells, Cultured, Dopamine metabolism, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Epigenesis, Genetic drug effects, Epigenesis, Genetic genetics, Histone Deacetylase Inhibitors, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Neurons cytology, Neurons drug effects, Oligodendrocyte Transcription Factor 2, Oligodendroglia drug effects, Oligodendroglia metabolism, Prosencephalon cytology, Prosencephalon drug effects, Rats, Rats, Wistar, Spheroids, Cellular, Stem Cells cytology, Stem Cells drug effects, Tubulin drug effects, Tubulin metabolism, gamma-Aminobutyric Acid metabolism, Cell Differentiation physiology, Cell Proliferation drug effects, Histone Deacetylases metabolism, Neurons enzymology, Prosencephalon enzymology, Stem Cells enzymology
- Abstract
Chromatin modification plays a key role in fate decision of neural stem cells. Here, we explored the impact of epigenetic remodelling onto neuronal fate determination using specific inhibitors of histone deacetylases (iHDAC). Adult subventricular zone (SVZ) precursor cells were expanded as neurospheres and treated in vitro with second generation iHDAC MS-275, M344 and suberoylanilide hydroxamic acid (SAHA). All tested compounds revealed a significant increase of betaIII-tubulin positive neurons (ranging from 258 to 431%) in a concentration-dependent manner. The number of oligodendrocytes was decreased by almost 50%, accompanied by a reduction of Olig2 mRNA expression. In contrast, astrocyte quantity remained unaffected after iHDAC treatment. Both control and iHDAC treated cells expressed markers of mature GABAergic and dopaminergic neurons. Increased expression levels of NeuroD, Cyclin D2 and B-lymphocyte translocation gene 3 (Btg3) point to a shift towards neuronal fate determination targeted by HDAC inhibitors.
- Published
- 2007
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