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

Scientific Reports
Hui-Juan JinBo Hu

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...Continue Reading

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Citations

Aug 20, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jiayi ZhuBo Hu
Sep 9, 2018·Journal of Natural Medicines·Changde WangXiao Cheng
Nov 10, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Tao LiYongmei Yan
Feb 10, 2019·Molecular Neurobiology·John Q Wang, Limin Mao
Sep 19, 2020·International Journal of Molecular Sciences·Mojgan GharipourShayesteh Jahanfar
Aug 19, 2020·Annals of the New York Academy of Sciences·Chi Him PoonLee Wei Lim
Oct 26, 2018·Current Neurology and Neuroscience Reports·F CholletI Loubinoux
Sep 2, 2020·European Journal of Pharmacology·Maciej KorczakMagdalena Bujalska-Zadrożny
Nov 9, 2020·Behavioural Brain Research·Yufang SiZhongliang Zhu
Feb 26, 2019·Journal of Affective Disorders·Laura M HackBoadie W Dunlop
Apr 4, 2021·Journal of Personalized Medicine·Piotr CzarnyTomasz Sliwinski
Mar 31, 2021·Biochemical and Biophysical Research Communications·Qingqing YinBin Liu

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Methods Mentioned

BETA
pharmacotherapy
immunoprecipitation
co-immunoprecipitation
transfection
Co-IP
fluorescence microscopy
ChIP
PCR

Software Mentioned

Methprimer
Epityper

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