miR-34b-3p Inhibition of eIF4E Causes Post-stroke Depression in Adult Mice.
10.1007/s12264-022-00898-7
- Author:
Xiao KE
1
;
Manfei DENG
1
;
Zhuoze WU
2
;
Hongyan YU
1
;
Dian YU
1
;
Hao LI
1
;
Youming LU
3
;
Kai SHU
4
;
Lei PEI
5
Author Information
1. Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
2. Department of Pathophysiology, Basic Medical School, North Sichuan Medical College, Nanchong, 637100, China.
3. The Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China.
4. Department of Neurosurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
5. Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. peilei@hust.edu.cn.
- Publication Type:Journal Article
- Keywords:
Hippocampus;
Microglia;
Neuroinflammation;
Post-stroke depression;
miRNA
- MeSH:
Animals;
Mice;
Depression;
Eukaryotic Initiation Factor-4E/metabolism*;
MicroRNAs/metabolism*;
Neurons/metabolism*;
Stroke/metabolism*
- From:
Neuroscience Bulletin
2023;39(2):194-212
- CountryChina
- Language:English
-
Abstract:
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.
