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Histone deacetylase inhibitors increase neuronal differentiation in adult forebrain precursor cells

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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 βIII-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.

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Acknowledgments

The authors thank D. Müller for excellent technical assistance. This work has been supported by the Bavarian Research Council (Munich) and the Johannes and Frieda Marohn Foundation (University of Erlangen). FAS is a fellow of the Studienstiftung des deutschen Volkes e.V. (German national merit foundation).

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Authors and Affiliations

  1. Department of Neuropathology, University of Erlangen-Nuremberg, Krankenhausstr. 8–10, 91054, Erlangen, Germany

    Florian A. Siebzehnrubl, Rolf Buslei, Eric Hahnen & Ingmar Blumcke

  2. Department of Neurosurgery, University of Erlangen-Nuremberg, Erlangen, Germany

    Ilker Y. Eyupoglu

  3. Institute of Genetics, Institute of Human Genetics and Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany

    Sebastian Seufert & Eric Hahnen

Authors
  1. Florian A. Siebzehnrubl
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  2. Rolf Buslei
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  3. Ilker Y. Eyupoglu
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  4. Sebastian Seufert
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  5. Eric Hahnen
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  6. Ingmar Blumcke
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Correspondence to Florian A. Siebzehnrubl.

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Siebzehnrubl, F.A., Buslei, R., Eyupoglu, I.Y. et al. Histone deacetylase inhibitors increase neuronal differentiation in adult forebrain precursor cells. Exp Brain Res 176, 672–678 (2007). https://doi.org/10.1007/s00221-006-0831-x

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  • DOI: https://doi.org/10.1007/s00221-006-0831-x

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