Department of Biochemistry and Molecular Biology, Hanyang University, Seoul, Korea.
Mol Cells. 2011 Feb;31(2):159-64. doi: 10.1007/s10059-011-0019-5. Epub 2010 Dec 22.
Histone deacetylase inhibitors (HDACIs) that modulate gene expression by inhibiting HDAC enzymes may contribute to the survival of immature hippocampal neurons. However, it remains unknown how and when HDACIs regulate the survival of newly generated immature hippocampal neurons. In the present study, if the treatment of valproic acid (VPA) and sodium butyrate (SBt) in the specific time window during the development of newly generated n eurons r esulted in the i ncreased survival of bromodeoxyuridine (BrdU)(+) neurons in the dentate gyrus (DG) of hippocampus in mice was investigated. It was found that the number of BrdU(+) cells, the expressions of anti-apoptotic Bcl-2 family members and pCREB [D1] were increased by HDACIs when HDACIs were treated no later than 2-3 weeks after BrdU labeling. This suggests that epigenetic modification within a specific time window is critical for the survival of newborn hippocampal neurons by inhibiting the apoptotic pathway.
组蛋白去乙酰化酶抑制剂(HDACIs)通过抑制 HDAC 酶来调节基因表达,可能有助于不成熟海马神经元的存活。然而,目前尚不清楚 HDACIs 如何以及何时调节新生成的不成熟海马神经元的存活。在本研究中,研究了在新生神经元发育过程中特定时间窗内给予丙戊酸(VPA)和丁酸钠(SBt)治疗是否导致小鼠海马齿状回(DG)中 BrdU(+)神经元的存活增加。结果发现,HDACIs 治疗时间不晚于 BrdU 标记后 2-3 周,可增加 BrdU(+)细胞数量、抗凋亡 Bcl-2 家族成员和 pCREB [D1]的表达。这表明在特定时间窗内进行表观遗传修饰对于通过抑制凋亡途径来维持新生海马神经元的存活至关重要。