PMID- 28473755
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 11
DP  - 2017
TI  - The Combination of Long-term Ketamine and Extinction Training Contributes to Fear 
      Erasure by Bdnf Methylation.
PG  - 100
LID - 10.3389/fncel.2017.00100 [doi]
LID - 100
AB  - A combination of antidepressant drugs and psychotherapy exhibits more promising 
      efficacy in treating fear disorders than either treatment alone, but underlying 
      mechanisms of such treatments remain largely unknown. Here we investigated the 
      role of DNA methylation of the brain-derived neurotrophic factor (Bdnf) gene in 
      the therapeutic effects of ketamine in combination with extinction training in a 
      mouse model of post-traumatic stress disorder (PTSD) induced by inescapable 
      electric foot shocks (IFS). Male mice received ketamine for 22 consecutive days 
      starting 1 h after the IFS (long-term ketamine treatment) or 2 h prior to the 
      extinction training on days 15 and 16 after the IFS (short-term ketamine 
      treatment). The Open Field (OF) and Elevated Plus Maze (EPM) tests were conducted 
      on days 18 and 20. The spontaneous recovery and fear renewal tests were performed 
      on day 23. Mice, subjected to IFS, exhibited anxiety-like behavior and fear 
      relapse, accompanied by the increased levels of DNA methyltransferases, 
      hyper-methylation of Bdnf gene, and decreased BDNF mRNA expression in the medial 
      prefrontal cortex (mPFC) and hippocampus (HIP). Long-term treatment with ketamine 
      combined with extinction training alleviated the IFS-induced abnormalities. These 
      results suggest that long-term ketamine treatment in combination with extinction 
      training may ameliorate fear relapse in the murine model of PTSD, at least in 
      part, by normalizing DNA methylation of Bdnf gene.
FAU - Ju, Ling-Sha
AU  - Ju LS
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
FAU - Yang, Jiao-Jiao
AU  - Yang JJ
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
AD  - Department of Anesthesiology and the McKnight Brain Institute, University of 
      Florida College of MedicineGainesville, FL, USA.
FAU - Lei, Lei
AU  - Lei L
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
FAU - Xia, Jiang-Yan
AU  - Xia JY
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
FAU - Luo, Dan
AU  - Luo D
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
FAU - Ji, Mu-Huo
AU  - Ji MH
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
FAU - Martynyuk, Anatoly E
AU  - Martynyuk AE
AD  - Department of Anesthesiology and the McKnight Brain Institute, University of 
      Florida College of MedicineGainesville, FL, USA.
FAU - Yang, Jian-Jun
AU  - Yang JJ
AD  - Department of Anesthesiology, Zhongda Hospital, Medical School, Southeast 
      UniversityNanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20170420
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC5398013
OTO - NOTNLM
OT  - BDNF
OT  - DNA methylation
OT  - extinction
OT  - inescapable foot shocks
OT  - ketamine
EDAT- 2017/05/06 06:00
MHDA- 2017/05/06 06:01
PMCR- 2017/01/01
CRDT- 2017/05/06 06:00
PHST- 2017/01/15 00:00 [received]
PHST- 2017/03/27 00:00 [accepted]
PHST- 2017/05/06 06:00 [entrez]
PHST- 2017/05/06 06:00 [pubmed]
PHST- 2017/05/06 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2017.00100 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2017 Apr 20;11:100. doi: 10.3389/fncel.2017.00100. 
      eCollection 2017.