摘要
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。
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.
作者
孔传祥
薛世磊
马福兴
Kong Chuanxiang;Xue Shilei;Ma Fuxing(Department of Neurosurgery,the Second People's Hospital of Xining,Xining 810003,China)
出处
《神经疾病与精神卫生》
2019年第10期931-935,共5页
Journal of Neuroscience and Mental Health
