Suppression of microRNA-9-5p rescues learning and memory in chronic cerebral hypoperfusion rats model.
Suppression of microRNA-9-5p rescues learning and memory in chronic cerebral hypoperfusion rats model.
复制标题
抑制microRNA-9-5p可挽救慢性脑低灌注大鼠模型的学习和记忆
DOI：
10.18632/oncotarget.22415
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发表时间：
2017-12-08
期刊：
影响因子：
--
通讯作者：
Chen KS
中科院分区：
文献类型：
--
作者：
Wei N;Zheng K;Xue R;Ma SL;Ren HY;Huang HF;Wang WW;Xu JJ;Chen KS
慢性脑灌注不足与痴呆中的认知障碍有关，如阿尔茨海默病（AD）和血管病（VaD），这是老年人中两种最常见的神经退行性疾病。然而，AD和VaD的有效治疗方法仍然缺失。microRNA（miRNAs）是一类在神经系统疾病的表观遗传调控中发挥重要作用的非编码小分子RNA，其调控异常在AD和VaD中均发挥重要作用。在本研究中，我们报道了miR-9- 5 p在VaD患者的血清和脑脊液中升高。miR-9- 5 p在双血管闭塞手术大鼠的海马和皮质中也增加。此外，miR-9- 5 p抑制剂的应用减轻了在Morris水迷宫和抑制性回避下降任务中具有2血管闭塞手术的大鼠的记忆障碍。此外，miR-9- 5 p抑制剂可减轻慢性脑低灌注大鼠长时程增强的抑制和树突棘的丢失。此外，胆碱能神经元功能被miR-9- 5 p抑制剂挽救，以及神经元损失和氧化应激。我们得出结论，miR-9- 5 p抑制可能是慢性脑灌注不足引起的记忆障碍的潜在治疗靶点。
Chronic cerebral hypoperfusion has been associated with cognitive impairment in dementias, such as Alzheimer's disease (AD) and vascular disease (VaD), the two most common neurodegenerative diseases in aged people. However, the effective therapeutic approaches for both AD and VaD are still missing. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in the epigenetic regulation in many neurological disorders; the critical roles of miRNAderegulation had been implicated in both AD and VaD. In the current study, we reported that miR-9-5p is elevated in the serum and cerebrospinalfluid of patientswith VaD. The miR-9-5p wasalso increased in both the hippocampus and cortex of rats with 2-vessel occlusionsurgery. Furthermore, application ofmiR-9-5p antagomirs attenuated the memory impairments in rats with 2-vessel occlusion surgery both in the Morris water maze and inhibitory avoidance step-down tasks. Furthermore, miR-9-5p antagomirs reducedthe inhibition oflong-term potentiation and loss of dendritic spines in chronic cerebral hypoperfusionrats. Additionally, the cholinergic neuronal function was rescued by miR-9-5p antagomirs, as well as the neuronal loss and the oxidative stress. We concluded that miR-9-5p inhibition may be a potential therapeutic target for the memory impairments caused by chronic cerebral hypoperfusion.
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DOI：
10.1111/j.1749-6632.2010.05732.x
发表时间：
2010-01-01
期刊：
INNATE INFLAMMATION AND STROKE
影响因子：
--
作者：
Melani, Alessia;Cipriani, Sara;Pedata, Felicita
通讯作者：
Pedata, Felicita
影响因子：
4
作者：
Femminella GD;Ferrara N;Rengo G
通讯作者：
Rengo G
影响因子：
5.1
作者：
Hu, Juan;Huang, He-Zhou;Zhu, Ling-Qiang
通讯作者：
Zhu, Ling-Qiang
影响因子：
4.7
作者：
Lucena, Greice M.;Prediger, Rui D.;Ferreira, Vania M.
通讯作者：
Ferreira, Vania M.
影响因子：
16.2
作者：
Iadecola C
通讯作者：
Iadecola C