Alleviative effects of fluoxetine on depressive-like behaviors by epigenetic regulation of BDNF gene transcription in mouse model of post-stroke depression

Hui Juan Jin, Lei Pei, Ya Nan Li, Hui Zheng, Shuai Yang, Yan Wan, Ling Mao, Yuan Peng Xia, Quan Wei He, Man Li, Zhen Yu Yue, Bo Hu

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Fluoxetine, one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, has been thought to be effective for treating post-stroke depression (PSD). Recent work has shown that fluoxetine may exert an antidepressive effect through increasing the level of brain-derived neurotrophic factor (BDNF), but the underlying mechanism still remains unclear. In the present study, we successfully established the PSD model using male C57BL/6 J mice by photothrombosis of the left anterior cortex combined with isolatied-housing conditions. In the process, we confirmed that fluoxetine could improve the depression-like behaviors of PSD mice and upregulate the expression of BDNF in the hippocampus. However, depletion of BDNF by transfecting lentivirus-derived shBDNF in hippocampus suppressed the effect of fluoxetine. Furthermore, we demonstrated the epigenetic mechanisms involved in regulation of BDNF expression induced by fluoxetine. We found a statistically significant increase in DNA methylation at specific CpG sites (loci 2) of Bdnf promoter IV in the hippocampus of PSD mice. We also found that fluoxetine treatment could disassociate the MeCP2-CREB-Bdnf promoter IV complex via phosphorylation of MeCP2 at Ser421 by Protein Kinase A (PKA). Our research highlighted the importance of fluoxetine in regulating BDNF expression which could represent a potential strategy for preventing PSD.

Original languageEnglish
Article number14926
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - 1 Dec 2017

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