Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer's Disease.
Replenishment of microRNA-188-5p restores the synaptic and cognitive deficits in 5XFAD Mouse Model of Alzheimer's Disease.
复制标题
DOI：
10.1038/srep34433
复制
发表时间：
2016-10-06
影响因子：
4.6
通讯作者：
Kim HS
中科院分区：
文献类型：
--
作者：
Lee K;Kim H;An K;Kwon OB;Park S;Cha JH;Kim MH;Lee Y;Kim JH;Cho K;Kim HS
MicroRNA 已成为中枢神经系统发育、神经发生和突触功能的关键因素。在本研究中，我们研究了 microRNA-188-5p (miR-188-5p) 在阿尔茨海默病 (AD) 中的病理生理学意义。我们发现寡聚 Aβ1-42 治疗减少了原代海马神经元培养物中 miR-188-5p 的表达，并且 miR-188-5p 挽救了 Aβ1-42 介导的突触消除和突触功能障碍。此外，在 7 个月大的五只家族性 AD (5XFAD) 转基因小鼠中观察到的认知功能和突触传递损伤可通过病毒介导的 miR-188-5p 表达得到改善。 AD 患者和 5XFAD 小鼠脑组织中 miR-188-5p 表达下调。添加 miR-188-5p 可以挽救用寡聚 Aβ1-42 处理并从 5XFAD 小鼠培养的原代海马神经元中树突棘密度的降低。添加 miR-188-5p 也可以恢复 mEPSC 频率的降低。在 7 个月大的 5XFAD 小鼠中观察到的基础 fEPSP 和认知损伤通过海马中病毒介导的 miR-188-5p 表达得到改善。此外，我们发现 miR-188 的表达是 CREB 依赖性的。综上所述，我们的结果表明，miR-188-5p 表达失调通过诱导与 Aβ 介导的病理生理学相关的突触功能障碍和认知缺陷，从而促进 AD 的发病机制。
MicroRNAs have emerged as key factors in development, neurogenesis and synaptic functions in the central nervous system. In the present study, we investigated a pathophysiological significance of microRNA-188-5p (miR-188-5p) in Alzheimer’s disease (AD). We found that oligomeric Aβ1-42 treatment diminished miR-188-5p expression in primary hippocampal neuron cultures and that miR-188-5p rescued the Aβ1-42-mediated synapse elimination and synaptic dysfunctions. Moreover, the impairments in cognitive function and synaptic transmission observed in 7-month-old five familial AD (5XFAD) transgenic mice, were ameliorated via viral-mediated expression of miR-188-5p. miR-188-5p expression was down-regulated in the brain tissues from AD patients and 5XFAD mice. The addition of miR-188-5p rescued the reduction in dendritic spine density in the primary hippocampal neurons treated with oligomeric Aβ1-42 and cultured from 5XFAD mice. The reduction in the frequency of mEPSCs was also restored by addition of miR-188-5p. The impairments in basal fEPSPs and cognition observed in 7-month-old 5XFAD mice were ameliorated via the viral-mediated expression of miR-188-5p in the hippocampus. Furthermore, we found that miR-188 expression is CREB-dependent. Taken together, our results suggest that dysregulation of miR-188-5p expression contributes to the pathogenesis of AD by inducing synaptic dysfunction and cognitive deficits associated with Aβ-mediated pathophysiology in the disease.
登录
查看更多内容
影响因子：
56.9
作者：
Kim, Jongpil;Inoue, Keiichi;Abeliovich, Asa
通讯作者：
Abeliovich, Asa
DOI：
10.1073/pnas.0710263105
发表时间：
2008-04-29
影响因子：
11.1
作者：
Hebert, Sebastien S.;Horre, Katrien;De Strooper, Bart
通讯作者：
De Strooper, Bart
影响因子：
16.2
作者：
Chen, H;Bagri, A;Tessier-Lavigne, M
通讯作者：
Tessier-Lavigne, M
影响因子：
2.6
作者：
Chen, CY;Li, M;Yao, QH
通讯作者：
Yao, QH
DOI：
10.1073/pnas.1017576108
发表时间：
2011-07-12
影响因子：
11.1
作者：
Cohen, Jonathan E.;Lee, Philip R.;Fields, R. Douglas
通讯作者：
Fields, R. Douglas