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01-02-2007 | Research Note

Histone deacetylase inhibitors increase neuronal differentiation in adult forebrain precursor cells

Authors: Florian A. Siebzehnrubl, Rolf Buslei, Ilker Y. Eyupoglu, Sebastian Seufert, Eric Hahnen, Ingmar Blumcke

Published in: Experimental Brain Research | Issue 4/2007

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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Title: Histone deacetylase inhibitors increase neuronal differentiation in adult forebrain precursor cells
Authors: Florian A. Siebzehnrubl
Rolf Buslei
Ilker Y. Eyupoglu
Sebastian Seufert
Eric Hahnen
Ingmar Blumcke
Publication date: 01-02-2007
Publisher: Springer-Verlag
Published in: Experimental Brain Research / Issue 4/2007
Print ISSN: 0014-4819
Electronic ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-006-0831-x

At a glance: The STEP trials

Springer Medicine

Histone deacetylase inhibitors increase neuronal differentiation in adult forebrain precursor cells

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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