PMID- 29097744
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20190715
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Nov 2
TI  - Alleviative effects of fluoxetine on depressive-like behaviors by epigenetic 
      regulation of BDNF gene transcription in mouse model of post-stroke depression.
PG  - 14926
LID - 10.1038/s41598-017-13929-5 [doi]
LID - 14926
AB  - 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.
FAU - Jin, Hui-Juan
AU  - Jin HJ
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Pei, Lei
AU  - Pei L
AD  - Department of Neurobiology, School of Basic Medicine, Tongji Medical College, 
      Huahzong University of Science and Technology, Wuhan, 430030, China.
AD  - The Institute for Brain Research (IBR), Collaborative Innovation Center for Brain 
      Science, Huazhong University of Science and Technology, Wuhan, 430030, China.
FAU - Li, Ya-Nan
AU  - Li YN
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Zheng, Hui
AU  - Zheng H
AD  - Department of Radiology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Yang, Shuai
AU  - Yang S
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Wan, Yan
AU  - Wan Y
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Mao, Ling
AU  - Mao L
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Xia, Yuan-Peng
AU  - Xia YP
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - He, Quan-Wei
AU  - He QW
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Li, Man
AU  - Li M
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China.
FAU - Yue, Zhen-Yu
AU  - Yue ZY
AD  - Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine 
      at Mount Sinai, New York, New York, 10029, USA.
FAU - Hu, Bo
AU  - Hu B
AD  - Department of Neurology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan, 430022, China. 
      hubo@mail.hust.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171102
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 01K63SUP8D (Fluoxetine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/pharmacology/*therapeutic use
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Depression/*drug therapy/*etiology/genetics
MH  - Depressive Disorder/drug therapy/etiology/genetics
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic/*drug effects
MH  - Fluoxetine/pharmacology/*therapeutic use
MH  - Hippocampus/drug effects/metabolism
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Stroke/*complications
MH  - Transcriptional Activation/drug effects
PMC - PMC5668242
COIS- The authors declare that they have no competing interests.
EDAT- 2017/11/04 06:00
MHDA- 2019/07/16 06:00
PMCR- 2017/11/02
CRDT- 2017/11/04 06:00
PHST- 2017/04/06 00:00 [received]
PHST- 2017/10/03 00:00 [accepted]
PHST- 2017/11/04 06:00 [entrez]
PHST- 2017/11/04 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2017/11/02 00:00 [pmc-release]
AID - 10.1038/s41598-017-13929-5 [pii]
AID - 13929 [pii]
AID - 10.1038/s41598-017-13929-5 [doi]
PST - epublish
SO  - Sci Rep. 2017 Nov 2;7(1):14926. doi: 10.1038/s41598-017-13929-5.