TY - JOUR
T1 - Expression of Histone Deacetylases in Cellular Compartments of the Mouse Brain and the Effects of Ischemia
AU - Baltan, Selva
AU - Bachleda, Amelia
AU - Morrison, Richard S.
AU - Murphy, Sean P.
N1 - Funding Information:
Acknowledgments This work was supported by the American Heart Association (S.B.), National Institutes of Health (NIH)–National Institute on Aging grant AG033720 (S.B.), and NIH–National Institute of Neurological Disorders and Stroke grant NS065319 (S.P. M., R.S.M.). We thank Rona Lee for performing the mouse MCAo surgery.
PY - 2011/9
Y1 - 2011/9
N2 - Drugs that inhibit specific histone deacetylase (HDAC) activities have enormous potential in preventing the consequences of acute injury to the nervous system and in allaying neurodegeneration. However, very little is known about the expression pattern of the HDACs in the central nervous system (CNS). Identifying the cell types that express HDACs in the CNS is important for determining therapeutic targets for HDAC inhibitors and evaluating potential side effects. We characterized the cellular expression of HDACs 1-3, and HDACs 4 and 6, in the adult mouse brain in the cingulate cortex, parietal cortex, dentate gyrus, and CA1 regions of the hippocampus and subcortical white matter. Expression of class I HDACs showed a cell- and region-specific pattern. Transient focal ischemia induced by temporary middle cerebral artery occlusion, or global ischemia induced by in vitro oxygen-glucose deprivation, altered the extent of HDAC expression in a region- and cell-specific manner. The pan-HDAC inhibitor, SAHA, reduced ischemia-induced alterations in HDACs. The results suggest that in addition to promoting epigenetic changes in transcriptional activity in the nucleus of neurons and glia, HDACs may also have non-transcriptional actions in axons and the distant processes of glial cells and may significantly modulate the response to injury in a cell- and region-specific manner.
AB - Drugs that inhibit specific histone deacetylase (HDAC) activities have enormous potential in preventing the consequences of acute injury to the nervous system and in allaying neurodegeneration. However, very little is known about the expression pattern of the HDACs in the central nervous system (CNS). Identifying the cell types that express HDACs in the CNS is important for determining therapeutic targets for HDAC inhibitors and evaluating potential side effects. We characterized the cellular expression of HDACs 1-3, and HDACs 4 and 6, in the adult mouse brain in the cingulate cortex, parietal cortex, dentate gyrus, and CA1 regions of the hippocampus and subcortical white matter. Expression of class I HDACs showed a cell- and region-specific pattern. Transient focal ischemia induced by temporary middle cerebral artery occlusion, or global ischemia induced by in vitro oxygen-glucose deprivation, altered the extent of HDAC expression in a region- and cell-specific manner. The pan-HDAC inhibitor, SAHA, reduced ischemia-induced alterations in HDACs. The results suggest that in addition to promoting epigenetic changes in transcriptional activity in the nucleus of neurons and glia, HDACs may also have non-transcriptional actions in axons and the distant processes of glial cells and may significantly modulate the response to injury in a cell- and region-specific manner.
KW - Astrocytes
KW - Axon
KW - Dentate gyrus
KW - Neurogenesis
KW - Neurovascular unit
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U2 - 10.1007/s12975-011-0087-z
DO - 10.1007/s12975-011-0087-z
M3 - Article
C2 - 21966324
AN - SCOPUS:80052239705
SN - 1868-4483
VL - 2
SP - 411
EP - 423
JO - Translational Stroke Research
JF - Translational Stroke Research
IS - 3
ER -