PMID- 30096331
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20190318
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Linking)
VI  - 88
DP  - 2019 Jan 10
TI  - Spontaneous resurgence of conditioned fear weeks after successful extinction in 
      brain injured mice.
PG  - 276-286
LID - S0278-5846(18)30307-5 [pii]
LID - 10.1016/j.pnpbp.2018.07.023 [doi]
AB  - Mild traumatic brain injury (TBI) is a major risk factor for post-traumatic 
      stress disorder (PTSD), and both disorders share common symptoms and 
      neurobiological defects. Relapse after successful treatment, known as long-term 
      fear resurgence, is common in PTSD patients and a major therapeutic hurdle. We 
      induced a mild focal TBI by controlled cortical impact (CCI) in male C57BL/6 J 
      mice and used fear conditioning to assess PTSD-like behaviors and concomitant 
      alterations in the fear circuitry. We found for the first time that mild TBI, and 
      to a lesser extent sham (craniotomy), mice displayed a spontaneous resurgence of 
      conditioned fear when tested for fear extinction memory recall, despite having 
      effectively acquired and extinguished conditioned fear 6 weeks earlier in the 
      same context. Other characteristic symptoms of PTSD are risk-taking behaviors and 
      cognitive deficits. CCI mice displayed risk-taking behaviors, behavioral 
      inflexibility and reductions in processing speed compared to naive mice. In 
      conjunction with these changes there were alterations in amygdala morphology 
      3 months post-trauma, and decreased myelin basic protein density at the primary 
      lesion site and in distant secondary sites such as the hippocampus, thalamus, and 
      amygdala, compared to sham mice. Furthermore, activity-dependent brain-derived 
      neurotrophic factor (BDNF) transcripts were decreased in the prefrontal cortex, a 
      key region for fear extinction consolidation, following fear extinction training 
      in both TBI and, to a lesser extent, sham mice. This study shows for the first 
      time that a mild brain injury can generate a spontaneous resurgence of 
      conditioned fear associated with defective BDNF signalling in the prefrontal 
      cortex, PTSD-like behaviors, and have enduring effects on the brain.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Corne, R
AU  - Corne R
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Leconte, C
AU  - Leconte C
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Ouradou, M
AU  - Ouradou M
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Fassina, V
AU  - Fassina V
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Zhu, Y
AU  - Zhu Y
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Deou, E
AU  - Deou E
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Besson, V
AU  - Besson V
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Plotkine, M
AU  - Plotkine M
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Marchand-Leroux, C
AU  - Marchand-Leroux C
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France.
FAU - Mongeau, R
AU  - Mongeau R
AD  - EA4475 - Pharmacologie de la Circulation Cerebrale, Faculte de Pharmacie de 
      Paris, Universite Paris Descartes, Paris, France. Electronic address: 
      raymond.mongeau@parisdescartes.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180807
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Myelin Basic Protein)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Brain Injuries/pathology/*physiopathology/*psychology
MH  - Conditioning, Classical/*physiology
MH  - Disease Models, Animal
MH  - Extinction, Psychological/*physiology
MH  - Fear/*physiology
MH  - Male
MH  - Maze Learning
MH  - Mental Recall
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myelin Basic Protein/genetics/metabolism
MH  - Psychomotor Disorders/etiology
MH  - RNA, Messenger/metabolism
MH  - Risk-Taking
MH  - Statistics, Nonparametric
MH  - Time Factors
OTO - NOTNLM
OT  - Barnes maze
OT  - Brain derived neurotrophic factor
OT  - Fear conditioning
OT  - Myelin basic protein
OT  - Post-traumatic stress disorder
OT  - Risk-taking behaviors
EDAT- 2018/08/11 06:00
MHDA- 2019/03/19 06:00
CRDT- 2018/08/11 06:00
PHST- 2018/04/23 00:00 [received]
PHST- 2018/06/28 00:00 [revised]
PHST- 2018/07/29 00:00 [accepted]
PHST- 2018/08/11 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
PHST- 2018/08/11 06:00 [entrez]
AID - S0278-5846(18)30307-5 [pii]
AID - 10.1016/j.pnpbp.2018.07.023 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2019 Jan 10;88:276-286. doi: 
      10.1016/j.pnpbp.2018.07.023. Epub 2018 Aug 7.