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. 2012 Jan;37(1):223-31. doi: 10.1007/s11064-011-0597-9. Epub 2011 Oct 5.
We previously reported that sodium butyrate (SB), a histone deacetylase inhibitor, robustly increased pyridoxine-induced cell proliferation and neuroblast differentiation in the dentate gyrus of the adult mouse. In this study, we investigated the effects of treatment with SB combined with pyridoxine on cell proliferation and neuroblast differentiation in the dentate gyrus of a mouse model of aging induced by D: -galactose (D: -gal). D: -gal was administered to 20-week-old male mice (D: -gal mice) for 10 weeks to induce changes that resemble natural aging in animals. Seven weeks after D: -gal (100 mg/kg) treatment, vehicle (physiological saline; D: -gal-vehicle mice) and SB (300 mg/kg) combined with pyridoxine (Pyr; 350 mg/kg) were administered to the mice (D: -gal-Pyr-SB mice) for 3 weeks. Escape latency under water maze in the D: -gal mice was longer than that in the control mice. In the D: -gal-Pyr-SB mice, escape latency was similar to that in the control mice. In the D: -gal mice, many cells in the granule cell layer of the dentate gyrus showed pyknosis and condensation of the cytoplasm. However, in the D: -gal-Pyr-SB mice, such cellular changes were rarely found. Furthermore, the D: -gal mice showed a great reduction in cell proliferation (Ki67-positive cells) and neuroblast differentiation (doublecortin-positive neuroblasts) in the dentate gyrus compared to control mice. However, in the D: -gal-Pyr-SB mice, cell proliferation and neuroblast differentiation were markedly increased in the dentate gyrus. Furthermore, the administration of pyridoxine with sodium butyrate significantly increased Ser133-phosphorylated cyclic AMP response element binding protein in the dentate gyrus. These results indicate that the combination treatment of Pyr with SB in D: -gal mice ameliorated the D: -gal-induced reduction in cell proliferation, neuroblast differentiation, and memory deficits.
我们之前曾报道过，组蛋白去乙酰化酶抑制剂丁酸钠（SB）可显著增强吡哆醇诱导的成年小鼠齿状回细胞增殖和神经母细胞分化。在这项研究中，我们研究了 SB 联合吡哆醇治疗对 D：-半乳糖（D：-gal）诱导的衰老小鼠模型齿状回细胞增殖和神经母细胞分化的影响。D：-gal 被给予 20 周龄雄性小鼠（D：-gal 小鼠）10 周以诱导类似于动物自然衰老的变化。D：-gal（100mg/kg）处理 7 周后，给予载体（生理盐水；D：-gal-vehicle 小鼠）和 SB（300mg/kg）联合吡哆醇（Pyr；350mg/kg）治疗小鼠（D：-gal-Pyr-SB 小鼠）3 周。D：-gal 小鼠在水迷宫中的逃避潜伏期长于对照小鼠。在 D：-gal-Pyr-SB 小鼠中，逃避潜伏期与对照小鼠相似。在 D：-gal 小鼠中，齿状回颗粒细胞层中的许多细胞出现固缩和细胞质浓缩。然而，在 D：-gal-Pyr-SB 小鼠中，很少发现这种细胞变化。此外，D：-gal 小鼠在齿状回中的细胞增殖（Ki67 阳性细胞）和神经母细胞分化（双皮质素阳性神经母细胞）显著减少，与对照小鼠相比。然而，在 D：-gal-Pyr-SB 小鼠中，齿状回中的细胞增殖和神经母细胞分化明显增加。此外，SB 联合吡哆醇给药可显著增加 D：-gal 小鼠齿状回中 Ser133 磷酸化环 AMP 反应元件结合蛋白。这些结果表明，在 D：-gal 小鼠中，Pyr 联合 SB 的联合治疗改善了 D：-gal 诱导的细胞增殖、神经母细胞分化和记忆缺陷。
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