Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, South Korea.
Neurochem Res. 2011 Oct;36(10):1850-7. doi: 10.1007/s11064-011-0503-5. Epub 2011 May 20.
We previously observed that pyridoxine (vitamin B(6)) significantly increased cell proliferation and neuroblast differentiation without any neuronal damage in the hippocampus. In this study, we investigated the effects of sodium butyrate, a histone deacetylase (HDAC) inhibitor which serves as an epigenetic regulator of gene expression, on pyridoxine-induced neural proliferation and neurogenesis induced by the increase of neural proliferation in the mouse dentate gyrus. Sodium butyrate (300 mg/kg, subcutaneously), pyridoxine (350 mg/kg, intraperitoneally), or combination with sodium butyrate were administered to 8-week-old mice twice a day and once a day, respectively, for 14 days. The administration of sodium butyrate significantly increased acetyl-histone H3 levels in the dentate gyrus. Sodium butyrate alone did not show the significant increase of cell proliferation in the dentate gyrus. But, pyridoxine alone significantly increased cell proliferation. Sodium butyrate in combination with pyridoxine robustly enhanced cell proliferation and neurogenesis induced by the increase of neural proliferation in the dentate gyrus, showing that sodium butyrate treatment distinctively enhanced development of neuroblast dendrites. These results indicate that an inhibition of HDAC synergistically promotes neurogenesis induced by a pyridoxine and increase of neural proliferation.
我们之前观察到，吡哆醇（维生素 B(6)）可在不损害海马神经元的情况下显著增加细胞增殖和神经母细胞分化。在这项研究中，我们研究了丁酸钠（一种组蛋白去乙酰化酶（HDAC）抑制剂，作为基因表达的表观遗传调节剂）对吡哆醇诱导的神经增殖以及由此引起的小鼠齿状回神经增殖增加所诱导的神经发生的影响。丁酸钠（300mg/kg，皮下注射）、吡哆醇（350mg/kg，腹腔注射）或两者联合，每天两次和每天一次分别给予 8 周龄小鼠，持续 14 天。丁酸钠给药可显著增加齿状回中的乙酰化组蛋白 H3 水平。丁酸钠单独给药不会导致齿状回中细胞增殖的显著增加。但是，吡哆醇单独给药可显著增加细胞增殖。丁酸钠与吡哆醇联合使用可显著增强齿状回中神经增殖引起的细胞增殖和神经发生，表明丁酸钠处理可显著增强神经母细胞树突的发育。这些结果表明，HDAC 抑制协同促进吡哆醇诱导的神经发生和神经增殖增加。
