Am J Stem Cell 2012;1(1):31-41

Original Article
HDAC9 is implicated in schizophrenia and expressed specifically in post-mitotic
neurons but not in adult neural stem cells

Bing Lang, Tahani Mohammed A Alrahbeni, David St Clair, Douglas H. Blackwood, International Schizophrenia Consortium, Colin D
McCaig, Sanbing Shen

School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK; Saudi Arabian
Ministry of Higher Education, Kingdom of Saudi Arabia; University of Edinburgh, Royal Edinburgh Hospital, Edinburgh EH10 5HF, UK;
Regenerative Medicine Institute, School of Medicine, National University of Ireland Galway, Newcastle Road, Ireland.

Received July 23, 2011; accepted August 10, 2011; Epub August 18, 2011; published January 1, 2012

Abstract: Schizophrenia is a common psychiatric disorder and caused by a combination of environmental, social and genetic factors.
Histone deacetylases (HDACs) can translate epigenetic effects to the genome by modifying chromatin structure and gene expression.
Inappropriate activity of HDACs is associated with cancer, cardiovascular and neurological diseases, and HDAC inhibitors are shown to
improve the derivation of induced pluripotent stem (iPS) cells and to modulate cell lineage differentiation during brain development. We
demonstrate that one of the HDAC genes, HDAC9, is hemizygously deleted in a small proportion of schizophrenia patients, and is widely
expressed in mouse brain including areas where the neuropathology of schizophrenia is found. High levels of expression are observed
in the hippocampus, layers II/III and V of the cerebral cortex, prefrontal and medial prefrontal cortex, piriform and cingulum cortex,
basolateral amygdaloid nuclei and choroid plexus. HDAC9 protein is found in the cell body as well as in nerve fibers. Importantly, HDAC9
is not expressed in adult neural stem cells, glia, astrocytes, or oligodendrocytes, but expressed exclusively in post-mitotic and mature
neurons. Our data suggest that HDAC9 may play a crucial role in neuronal function of adult brain. (AJSC1107002).

Keywords: Adult neural stem cells, copy number variation, HDAC9, histone deacetylase, neuron-specific expression, schizophrenia

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Address all correspondence to:
Dr. Colin D McCaig and Dr. Sanbing Shen
School of Medical Sciences
Institute of Medical Sciences
University of Aberdeen
Foresterhill, Aberdeen AB25 2ZD, UK;
E-mail: (CDM); (SS)
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