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 unavaila...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.展开更多
基金supported by the National Natural Science Foundation of China(81870932,81571078,51627807,31721002,81920208014,31930051)China Postdoctoral Science Foundation Funded Project(2020M672324,2020TQ0113).
文摘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.
