PMID- 19339601
OWN - NLM
STAT- MEDLINE
DCOM- 20090423
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 29
IP  - 13
DP  - 2009 Apr 1
TI  - Variant BDNF Val66Met polymorphism affects extinction of conditioned aversive 
      memory.
PG  - 4056-64
LID - 10.1523/JNEUROSCI.5539-08.2009 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays important roles in 
      activity-dependent plasticity processes, such as long-term potentiation, 
      learning, and memory. The recently reported human BDNF Val66Met (BDNF(Met)) 
      polymorphism has been shown to lead to altered hippocampal volume and impaired 
      hippocampal-dependent memory and is associated with a variety of neuropsychiatric 
      disorders. There are few studies, however, that investigate the effect of the 
      BDNF(Met) polymorphism on hippocampal-independent memory processes. A conditioned 
      taste aversion (CTA) task was used for studying the mechanisms of long-term, 
      hippocampal-independent, nondeclarative memory in the mammalian brain. Using the 
      CTA paradigm, we found a novel impairment in extinction learning, but not 
      acquisition or retention, of aversive memories resulting from the variant 
      BDNF(Met). BDNF(Met) mice were slower to extinguish an aversive CTA memory 
      compared with wild-type counterparts. Moreover, the BDNF(Met) was associated with 
      smaller volume and decreased neuronal dendritic complexity in the ventromedial 
      prefrontal cortex (vmPFC), which plays a significant role in extinction of CTA. 
      Finally, this delay in extinction learning could be rescued pharmacologically 
      with a cognitive enhancer, d-cycloserine (DCS). To our knowledge, this is the 
      first evidence that the BDNF(Met) polymorphism contributes to abnormalities in 
      memory extinction. This abnormality in extinction learning may be explained by 
      alterations in neuronal morphology, as well as decreased neural activity in the 
      vmPFC. Importantly, DCS was effective in rescuing this delay in extinction, 
      suggesting that when coupled with behavior therapy, DCS may be an effective 
      treatment option for anxiety disorders in humans with this genetic variant BDNF.
FAU - Yu, Hui
AU  - Yu H
AD  - Department of Neurobiology, School of Medicine, Shandong University, Jinan, 
      Shandong 250012, China.
FAU - Wang, Yue
AU  - Wang Y
FAU - Pattwell, Siobhan
AU  - Pattwell S
FAU - Jing, Deqiang
AU  - Jing D
FAU - Liu, Ting
AU  - Liu T
FAU - Zhang, Yun
AU  - Zhang Y
FAU - Bath, Kevin G
AU  - Bath KG
FAU - Lee, Francis S
AU  - Lee FS
FAU - Chen, Zhe-Yu
AU  - Chen ZY
LA  - eng
GR  - MH079513/MH/NIMH NIH HHS/United States
GR  - P50 MH079513-01A10001/MH/NIMH NIH HHS/United States
GR  - P50 MH079513/MH/NIMH NIH HHS/United States
GR  - R01 NS052819-04/NS/NINDS NIH HHS/United States
GR  - R01 NS052819/NS/NINDS NIH HHS/United States
GR  - MH060478/MH/NIMH NIH HHS/United States
GR  - NS052819/NS/NINDS NIH HHS/United States
GR  - R25 MH060478/MH/NIMH NIH HHS/United States
GR  - MH068850/MH/NIMH NIH HHS/United States
GR  - K08 MH068850/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 95IK5KI84Z (Cycloserine)
RN  - AE28F7PNPL (Methionine)
RN  - G4962QA067 (Lithium Chloride)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Animals
MH  - Avoidance Learning/drug effects/physiology
MH  - Behavior, Animal/physiology
MH  - Brain/drug effects/ultrastructure
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cycloserine/pharmacology
MH  - Extinction, Psychological/drug effects/*physiology
MH  - Food Preferences
MH  - Lithium Chloride/administration & dosage
MH  - Male
MH  - Memory/drug effects/*physiology
MH  - Methionine/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Polymorphism, Genetic/*genetics
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Silver Staining/methods
MH  - Taste/genetics
MH  - Time Factors
MH  - Valine/*genetics
PMC - PMC2668145
MID - NIHMS105407
EDAT- 2009/04/03 09:00
MHDA- 2009/04/25 09:00
PMCR- 2009/10/01
CRDT- 2009/04/03 09:00
PHST- 2009/04/03 09:00 [entrez]
PHST- 2009/04/03 09:00 [pubmed]
PHST- 2009/04/25 09:00 [medline]
PHST- 2009/10/01 00:00 [pmc-release]
AID - 3470024 [pii]
AID - 10.1523/JNEUROSCI.5539-08.2009 [doi]
PST - ppublish
SO  - J Neurosci. 2009 Apr 1;29(13):4056-64. doi: 10.1523/JNEUROSCI.5539-08.2009.