MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures.
MicroRNA-34b mediates hippocampal astrocyte apoptosis in a rat model of recurrent seizures.
复制标题
DOI：
10.1186/s12868-016-0291-6
复制
发表时间：
2016-08-11
期刊：
影响因子：
2.4
通讯作者：
Mao D
中科院分区：
文献类型：
--
作者：
Liu L;Liu L;Shi J;Tan M;Xiong J;Li X;Hu Q;Yi Z;Mao D
反复惊厥可导致不可逆的星形胶质细胞死亡，阻碍神经元再生，并进一步加重脑损伤。MicroRNAs已被发现在包括癌症和阿尔茨海默氏症在内的多种疾病的发展过程中扮演着重要角色。特别是，microRNA已被发现与癫痫诱导的神经元死亡有关。在这项研究中，利用氟乙基诱发反复惊厥的大鼠模型，评估了海马区组织中microRNA表达的变化。我们还应用了原代星形胶质细胞暴露于红藻氨酸的体外模型来验证动物模型中确定的miR-34b-5p的靶点。我们发现，miR-34家族成员miR-34b-5p在氟乙基处理的大鼠海马区组织中显著增加。更令人惊讶的是，这种上调与星形胶质细胞凋亡的积累同时发生，表明miR-34b-5p参与癫痫发作导致星形胶质细胞凋亡。体外实验结果进一步证明，miR-34b-5p可直接靶向Bcl-2mRNA，在翻译上抑制Bcl-2蛋白的表达，从而通过影响Bcl-2、Bax和Caspase-3来调节细胞的凋亡。我们的发现证明了microRNAs在反复惊厥诱导的星形胶质细胞死亡中发挥了作用，并进一步表明miR-34b-5p可能作为反复惊厥诱导的星形胶质细胞凋亡的调节因子。本文的在线版本(doi：10.1186/s12868-0160291-6)包含补充材料，授权用户可以使用。
Recurrent convulsions can cause irreversible astrocyte death, impede neuron regeneration, and further aggravate brain damage. MicroRNAs have been revealed as players in the progression of numerous diseases including cancer and Alzheimer’s disease. Particularly, microRNA has been found linked to seizure-induced neuronal death. In this study, a rat model of recurrent convulsions induced by flurothyl treatments was utilised to assess the alterations of microRNA expressions in hippocampus tissues. We also applied an in vitro model in which primary astrocytes were exposed to kainic acid to verify the targets of miR-34b-5p identified in the animal model. We discovered that miR-34b-5p, a member of the miR-34 family, increased significantly in flurothyl-treated rat hippocampus tissue. More surprisingly, this upregulation occurred concurrently with accumulating astrocyte apoptosis, indicating the involvement of miR-34b-5p in seizures caused astrocyte apoptosis. Results from the in vitro experiments further demonstrated that miR-34b-5p directly targeted Bcl-2 mRNA, translationally repressed Bcl-2 protein, and thus modulated cell apoptosis by influencing Bcl-2, Bax, and Caspase-3. Our findings prove microRNAs play a role in mediating recurrent convulsions-induced astrocyte death and further indicate that miR-34b-5p could acts as a regulator for astrocyte apoptosis induced by recurrent seizures. The online version of this article (doi:10.1186/s12868-016-0291-6) contains supplementary material, which is available to authorized users.