PMID- 30246290
OWN - NLM
STAT- MEDLINE
DCOM- 20200116
LR  - 20200930
IS  - 1601-183X (Electronic)
IS  - 1601-183X (Linking)
VI  - 18
IP  - 7
DP  - 2019 Sep
TI  - Combined brain-derived neurotrophic factor with extinction training alleviate 
      impaired fear extinction in an animal model of post-traumatic stress disorder.
PG  - e12520
LID - 10.1111/gbb.12520 [doi]
AB  - Impaired fear memory extinction (Ext) is one of the hallmark symptoms of 
      post-traumatic stress disorder (PTSD). However, since the precise mechanism of 
      impaired Ext remains unknown, effective interventions have not yet been 
      established. Recently, hippocampal-prefrontal brain-derived neurotrophic factor 
      (BDNF) activity was shown to be crucial for Ext in naive rats. We therefore 
      examined whether decreased hippocampal-prefrontal BDNF activity is also involved 
      in the Ext of rats subjected to a single prolonged stress (SPS) as a model of 
      PTSD. BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA), and 
      phosphorylation of TrkB was measured by immunohistochemistry in the hippocampus 
      and medial prefrontal cortex (mPFC) of SPS rats. We also examined whether BDNF 
      infusion into the ventral mPFC or hippocampus alleviated the impaired Ext of SPS 
      rats in the contextual fear conditioning paradigm. SPS significantly decreased 
      the levels of BDNF in both the hippocampus and mPFC and TrkB phosphorylation in 
      the ventral mPFC. Infusion of BDNF 24 hours after conditioning in the infralimbic 
      cortex (ILC), but not the prelimbic cortex (PLC) nor hippocampus, alleviated the 
      impairment of Ext. Since amelioration of impaired Ext by BDNF infusion did not 
      occur without extinction training, it seems the two interventions must occur 
      consecutively to alleviate impaired Ext. Additionally, BDNF infusion markedly 
      increased TrkB phosphorylation in the ILC of SPS rats. These findings suggest 
      that decreased BDNF signal transduction might be involved in the impaired Ext of 
      SPS rats, and that activation of the BDNF-TrkB signal might be a novel 
      therapeutic strategy for the impaired Ext by stress.
CI  - (c) 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics 
      Society.
FAU - Kataoka, Tsutomu
AU  - Kataoka T
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Fuchikami, Manabu
AU  - Fuchikami M
AUID- ORCID: 0000-0002-7759-6813
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Nojima, Shinji
AU  - Nojima S
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Nagashima, Nobuyuki
AU  - Nagashima N
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Araki, Motoaki
AU  - Araki M
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Omura, Jun
AU  - Omura J
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Miyagi, Tatsuhiro
AU  - Miyagi T
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Okamoto, Yasumasa
AU  - Okamoto Y
AD  - Department of Psychiatry and Neurosciences, Division of Frontier Graduate School 
      of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Morinobu, Shigeru
AU  - Morinobu S
AD  - Department of Occupational Therapy, School of Health Science and Social Welfare, 
      Kibi International University, Takahashi, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181009
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.10.1 (Ntrk2 protein, rat)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism/*therapeutic use
MH  - *Extinction, Psychological
MH  - Fear
MH  - Hippocampus/metabolism
MH  - Limbic System/metabolism
MH  - Male
MH  - Physical Conditioning, Animal/*methods
MH  - Prefrontal Cortex/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Stress Disorders, Post-Traumatic/drug therapy/*therapy
OTO - NOTNLM
OT  - animal model
OT  - brain-derived neurotrophic factor (BDNF)
OT  - extinction training
OT  - impaired extinction
OT  - post-traumatic stress disorder (PTSD)
EDAT- 2018/09/25 06:00
MHDA- 2020/01/17 06:00
CRDT- 2018/09/25 06:00
PHST- 2018/06/03 00:00 [received]
PHST- 2018/09/18 00:00 [revised]
PHST- 2018/09/18 00:00 [accepted]
PHST- 2018/09/25 06:00 [pubmed]
PHST- 2020/01/17 06:00 [medline]
PHST- 2018/09/25 06:00 [entrez]
AID - 10.1111/gbb.12520 [doi]
PST - ppublish
SO  - Genes Brain Behav. 2019 Sep;18(7):e12520. doi: 10.1111/gbb.12520. Epub 2018 Oct 
      9.