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

Xiao Ke1,2 • Manfei Deng1,2 • Zhuoze Wu3 • Hongyan Yu1,2 • Dian Yu1,2 • Hao Li1,2 • Youming Lu2,4 • Kai Shu5 • Lei Pei1,2

1 Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

2 The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, China

3 Department of Pathophysiology, Basic Medical School, North Sichuan Medical College, Nanchong 637100, China

4 Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

5 Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

 

Abstract

    Post-stroke depression (PSD) is a serious and common complication of stroke, which seriously afects the rehabilitation of stroke patients. To date, the pathogenesis of PSD is unclear and efective 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 signifcantly lower metabolic level than other brain regions. RNA sequencing revealed a signifcant 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 neuroinfammation, and abolished the depression-like behaviors in PSD mice. Together, our data demonstrated that insufcient 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.

 

 

Keywords

Post-stroke depression; Hippocampus; miRNA; Microglia; Neuroinfammation

 

[SpringerLink]