Abstract TMP71: Role Of Histone Deacetylases in Stroke-induced Oligodendrogenesis
Background: Histone deacetylases (HDACs) are a superfamily of isoforms that deacetylate lysine residues in histones. HDAC activity is essential for oligodendrocyte (OLG) differentiation. The present study measured spatial profiles of individual HDACs in white matter during brain repair after stroke.
Methods and Results: Adult male Wistar rats (n=8) were subjected to permanent right MCA occlusion and sacrificed 8 days later. Immunohistochemistry was performed on brain coronal sections with antibodies against HDACs, NG2 (a marker of oligodendrocyte progenitor cells, OPCs), and APC (a marker of OLGs). The numbers of immunoreactive cells were counted in peri-infarct and contralateral corpus callosum. Double immunofluorescent staining revealed that stroke significantly (p<0.05) increased the number of HDAC1 (HDAC1+/NG2+ cells, 166±7 vs.105±6 in contralateral), HDAC2 (HDAC2+/NG2+ cells, 130±4 vs. 98±2), and HDAC4 (HDAC4+/NG2+ cells, 74±5 vs. 56±4) positive OPCs, but did not significantly change HDAC5 positive OPCs. However, stroke only significantly increased the number of HDAC2 positive OLGs (HDAC2+/APC+ cells, 466 ±15 vs. 420±10), whereas the number of HDAC1 positive OLGs significantly decreased (HDAC1+/APC cells, 438±24 vs. 533±15, p<0.05). HDAC activity affects the acetylation (Ac) status of histone proteins (HH) within chromatin. We found stroke significantly decreased Ac-HH3+ OPCs (49±2 vs. 64±2) and Ac-HH3+ OLGs (311±16 vs. 356±13), which is consistent with elevation of HDAC activity in both cell types.
Conclusion: Our data indicate that stroke induces different expression profiles of class I (1 and 2) and II (4 and 5) HDACs in OPCs and OLGs, suggesting that these HDACs could play distinct roles in stroke-induced oligodendrogenesis.
- © 2012 by American Heart Association, Inc.