miR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice

miR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice
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miR-34b-3p 抑制 eIF4E 导致成年小鼠中风后抑郁

DOI:
10.1007/s12264-022-00898-7
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发表时间:
2022
期刊:
Springer Nature
影响因子:
--
通讯作者:
Lei Pei
Lei Pei
中科院分区:
其他
文献类型:
--
作者:
Xiao Ke;Manfei Deng;Zhuoze Wu;Hongyan Yu;Dian Yu;Hao Li;Youming Lu;Kai Shu;Lei Pei

文献摘要

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Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously affects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and effective treatments remain unavailable. Here, we established a mouse model of PSD through photothrombosis-induced focal ischemia. By using a combination of brain imaging, transcriptome sequencing, and bioinformatics analysis, we found that the hippocampus of PSD mice had a significantly lower metabolic level than other brain regions. RNA sequencing revealed a significant reduction of miR34b-3p, which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E (eIF4E). Furthermore, silencing eIF4E inactivated microglia, inhibited neuroinflammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufficient miR34b-3p after stroke cannot inhibit eIF4E translation, which causes PSD by the activation of microglia in the hippocampus. Therefore, miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.