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反复轻度创伤性脑损伤对大鼠海马组蛋白 去乙酰化酶功能的影响及其与学习记忆 能力的相关性
孔传祥薛世磊马福兴
()
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目的 探索反复轻度创伤性脑损伤(rMTBI)引起脑学习记忆能力下降与海马组蛋白去乙 酰化酶(HDACs)相关的分子机制。方法 采用 rMTBI 大鼠模型和新事物识别检测,分析大鼠 rMTBI 后 48 h 和 4 周时海马 HDAC 活性以及学习记忆能力的改变。使用泛 HDAC 抑制剂 trichostatin A(TSA)治疗, 观察 TSA 对 HDAC 活性及学习记忆能力的影响。结果 rMTBI 提高了不同时间点 HDAC2-5 和 HDAC11 亚型的 mRNA 水平,同时细胞核和细胞质内 HDAC 活性显著增加;然而,在损伤后 4 周时 HDAC8 的 mRNA 水 平 为(0.47±0.09),较 Sham 组(1.02±0.14)显 著 下 降(t=8.095,P< 0.001)。 给 予 TSA 治 疗 后, rMTBI 引起的学习记忆缺陷和 HDAC 活性均恢复了正常。结论 rMTBI 可能引起部分 HDAC 亚型的活 性上调而导致学习记忆能力受损,而 HDAC 活性抑制剂对 rMTBI 引起的认知缺陷治疗具有潜力。
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Effect of repeated mild traumatic brain injury on the function of histone deacetylase in hippocampus of rats
Kong Chuanxiang, Xue Shilei, Ma Fuxing
()
Abstract:
Objective To explore the molecular mechanism of hippocampal histone deacetylase (HDACs) related to the decline of brain learning and memory caused by repeated mild traumatic brain injury (rMTBI). Methods The changes of hippocampal HDAC activity and learning and memory ability at 48 hours and 4 weeks after rMTBI in rats were analyzed using the rat rMTBI model and new thing recognition detection. We used tricostatin A (TSA), a pan HDAC inhibitor, to observe the effect of TSA on HDAC activity and learning and memory ability. Results rMTBI increased the mRNA levels of different subtypes of HDAC 2-5 and HDAC 11 at different time points, with the increase of the activity of HDAC in nucleus and cytoplasm. However, compared with the Sham group (1.02±0.14), the mRNA level of HDAC8 decreased significantly to (0.47±0.09) 4 weeks after injury (t=8.095,P < 0.001). After treatment with TSA, the learning and memory deficit and HDAC activity caused by rmtbi returned to normal. Conclusions rMTBI may up-regulate the activity of some HDAC subtypes, resulting in impaired learning and memory ability, while HDAC activity inhibitors have potential in the treatment of cognitive defects caused by rMTB.

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