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

Xiao Ke ¹Manfei Deng ¹Zhuoze Wu ²Hongyan Yu ¹Dian Yu ¹Hao Li ¹Youming Lu ³Kai Shu ⁴Lei Pei¹

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作者信息

1. Department of Neurobiology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;The Institute for Brain Research,Collaborative Innovation Center for Brain Science,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;Department of Physiology,School of Basic Medicine,Tongji Medical College,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
折叠

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 sequenc-ing 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.

Key words

Post-stroke depression/Hippocampus/miRNA/Microglia/Neuroinflammation

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基金项目

University of Birmingham for English language editing()

National Natural Science Foundation of China(81870932)

National Natural Science Foundation of China(81571078)

National Natural Science Foundation of China(51627807)

National Natural Science Foundation of China(31721002)

National Natural Science Foundation of China(81920208014)

National Natural Science Foundation of China(31930051)

China Postdoctoral Science Foundation Funded Project(2020M672324)

China Postdoctoral Science Foundation Funded Project(2020TQ0113)

出版年

2023

神经科学通报(英文版)

中国科学院上海生命科学研究院

神经科学通报(英文版)

CSTPCDCSCD

影响因子：0.741

ISSN：1673-7067

参考文献量66

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