Laboratory of Molecular Neurobiology, Academy of Biology and Biotechnology, Southern Federal University, 194/1 Stachky Ave., Rostov-on-Don, Russia, 344090.
Mol Neurobiol. 2020 Jan;57(1):226-238. doi: 10.1007/s12035-019-01772-w. Epub 2019 Sep 6.
In ischemic stroke, vascular occlusion rapidly induces tissue infarct. Over the ensuing hours, damage spreads to adjacent tissue and forms transition zone (penumbra), which is potentially salvageable. Epigenetic regulation of chromatin structure controls gene expression and protein synthesis. We studied the expression of histone deacetylases HDAC1 and HDAC2 in the penumbra at 4 or 24 h after photothrombotic stroke (PTS) in the rat brain cortex. PTS increased the expression of HDAC1 and HDAC2 in penumbra and caused the redistribution of HDAC1 but not HDAC2 from the neuronal nuclei to cytoplasm. In astrocytes, HDAC1 expression and localization did not change. In neurons, HDAC2 localized exclusively in nuclei, but in astrocytes, it was also observed in processes. PTS induced neuronal apoptosis in the penumbra. TUNEL-stained apoptotic neurons co-localized with HDAC2 but not HDAC1. These data suggest that HDAC2 may represent the potential target for anti-stroke therapy and its selective inhibition may be a promising strategy for the protection of the penumbra tissue after ischemic stroke.
在缺血性中风中，血管阻塞会迅速导致组织梗死。在接下来的几个小时内，损伤会扩散到邻近组织，并形成过渡区（半影区），这是潜在可挽救的。染色质结构的表观遗传调控控制着基因表达和蛋白质合成。我们研究了大鼠大脑皮质光血栓性中风（PTS）后 4 或 24 小时半影区中组蛋白去乙酰化酶 HDAC1 和 HDAC2 的表达。PTS 增加了半影区中 HDAC1 和 HDAC2 的表达，并导致 HDAC1 从神经元核重新分布到细胞质，但 HDAC2 没有。在星形胶质细胞中，HDAC1 的表达和定位没有改变。在神经元中，HDAC2 仅定位于核内，但在星形胶质细胞中，也观察到其存在于突起中。PTS 在半影区诱导神经元凋亡。TUNEL 染色的凋亡神经元与 HDAC2 共定位，但与 HDAC1 不共定位。这些数据表明，HDAC2 可能是抗中风治疗的潜在靶点，其选择性抑制可能是缺血性中风后保护半影区组织的有前途的策略。
