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

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-induc...

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Bibliographic Details
Published in:Neuroscience bulletin 2023-02, Vol.39 (2), p.194-212
Main Authors: Ke, Xiao, Deng, Manfei, Wu, Zhuoze, Yu, Hongyan, Yu, Dian, Li, Hao, Lu, Youming, Shu, Kai, Pei, Lei
Format: Article
Language:English
Subjects:
Anatomy
Anesthesiology
Animals
Biomedical and Life Sciences
Biomedicine
Depression
Eukaryotic Initiation Factor-4E - genetics
Eukaryotic Initiation Factor-4E - metabolism
Genetic translation
Human Physiology
Ischemia
Mice
MicroRNAs - metabolism
Neurology
Neurons - metabolism
Neurophysiology
Neurosciences
Original
Original Article
Pain Medicine
RNA
RNA sequencing
Stroke (Disease)
Stroke - complications
Stroke - metabolism
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Summary: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.
ISSN:1673-7067
1995-8218
DOI:10.1007/s12264-022-00898-7