PMID- 22530815
OWN - NLM
STAT- MEDLINE
DCOM- 20121120
LR  - 20211203
IS  - 1601-183X (Electronic)
IS  - 1601-1848 (Print)
IS  - 1601-183X (Linking)
VI  - 11
IP  - 5
DP  - 2012 Jul
TI  - Fear extinction and BDNF: translating animal models of PTSD to the clinic.
PG  - 503-12
LID - 10.1111/j.1601-183X.2012.00801.x [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is the most studied neurotrophin 
      involved in synaptic plasticity processes that are required for long-term 
      learning and memory. Specifically, BDNF gene expression and activation of its 
      high-affinity tropomyosin-related kinase B (TrkB) receptor are necessary in the 
      amygdala, hippocampus and prefrontal cortex for the formation of emotional 
      memories, including fear memories. Among the psychiatric disorders with altered 
      fear processing, there is post-traumatic stress disorder (PTSD) which is 
      characterized by an inability to extinguish fear memories. Since BDNF appears to 
      enhance extinction of fear, targeting impaired extinction in anxiety disorders 
      such as PTSD via BDNF signalling may be an important and novel way to enhance 
      treatment efficacy. The aim of this review is to provide a translational point of 
      view that stems from findings in the BDNF regulation of synaptic plasticity and 
      fear extinction. In addition, there are different systems that seem to alter fear 
      extinction through BDNF modulation like the endocannabinoid system and the 
      hypothalamic-pituitary adrenal axis. Recent work also finds that the pituitary 
      adenylate cyclase-activating polypeptide and PAC1 receptor, which are upstream of 
      BDNF activation, may be implicated in PTSD. Especially interesting are data that 
      exogenous fear extinction enhancers such as antidepressants, histone deacetylases 
      inhibitors and D-cycloserine, a partial N-methyl d-aspartate agonist, may act 
      through or in concert with the BDNF-TrkB system. Finally, we review studies where 
      recombinant BDNF and a putative TrkB agonist, 7,8-dihydroxyflavone, may enhance 
      extinction of fear. These approaches may lead to novel agents that improve 
      extinction in animal models and eventually humans.
CI  - (c) 2012 The Authors. Genes, Brain and Behavior (c) 2012 Blackwell Publishing Ltd and 
      International Behavioural and Neural Genetics Society.
FAU - Andero, R
AU  - Andero R
AD  - Department of Psychiatry and Behavioral Sciences, Yerkes National Primate 
      Research Center, Emory University School of Medicine, Atlanta, GA, USA.
FAU - Ressler, K J
AU  - Ressler KJ
LA  - eng
GR  - R01 MH071537/MH/NIMH NIH HHS/United States
GR  - P51 OD011132/OD/NIH HHS/United States
GR  - P51OD11132/OD/NIH HHS/United States
GR  - R01 MH096764/MH/NIMH NIH HHS/United States
GR  - RC1 MH088467/MH/NIMH NIH HHS/United States
GR  - F32 MH085443/MH/NIMH NIH HHS/United States
GR  - F32MH085443/MH/NIMH NIH HHS/United States
GR  - K01 MH069884/MH/NIMH NIH HHS/United States
GR  - R01DA01962/DA/NIDA NIH HHS/United States
GR  - R01 DA019624/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120511
PL  - England
TA  - Genes Brain Behav
JT  - Genes, brain, and behavior
JID - 101129617
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - *Disease Models, Animal
MH  - Extinction, Psychological/*physiology
MH  - Fear/*physiology
MH  - Humans
MH  - Learning/physiology
MH  - Neuronal Plasticity/physiology
MH  - Stress Disorders, Post-Traumatic/*metabolism
MH  - Translational Research, Biomedical
PMC - PMC3389160
MID - NIHMS373778
EDAT- 2012/04/26 06:00
MHDA- 2012/12/10 06:00
PMCR- 2013/07/01
CRDT- 2012/04/26 06:00
PHST- 2012/04/26 06:00 [entrez]
PHST- 2012/04/26 06:00 [pubmed]
PHST- 2012/12/10 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - 10.1111/j.1601-183X.2012.00801.x [doi]
PST - ppublish
SO  - Genes Brain Behav. 2012 Jul;11(5):503-12. doi: 10.1111/j.1601-183X.2012.00801.x. 
      Epub 2012 May 11.