PMID- 22442074
OWN - NLM
STAT- MEDLINE
DCOM- 20120518
LR  - 20220316
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 32
IP  - 12
DP  - 2012 Mar 21
TI  - Variant brain-derived neurotrophic factor Val66Met polymorphism alters 
      vulnerability to stress and response to antidepressants.
PG  - 4092-101
LID - 10.1523/JNEUROSCI.5048-11.2012 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) plays important roles in cell survival, 
      neural plasticity, learning, and stress regulation. However, whether the recently 
      found human BDNF Val66Met (BDNF(Met)) polymorphism could alter stress 
      vulnerability remains controversial. More importantly, the molecular and 
      structural mechanisms underlying the interaction between the BDNF(Met) 
      polymorphism and stress are unclear. We found that heterozygous BDNF(+/Met) mice 
      displayed hypothalamic-pituitary-adrenal axis hyperreactivity, increased 
      depressive-like and anxiety-like behaviors, and impaired working memory compared 
      with WT mice after 7 d restraint stress. Moreover, BDNF(+/Met) mice exhibited 
      more prominent changes in BDNF levels and apical dendritic spine density in the 
      prefrontal cortex and amygdala after stress, which correlated with the impaired 
      working memory and elevated anxiety-like behaviors. Finally, the depressive-like 
      behaviors in BDNF(+/Met) mice could be selectively rescued by acute 
      administration of desipramine but not fluoxetine. These data indicate selective 
      behavioral, molecular, and structural deficits resulting from the interaction 
      between stress and the human genetic BDNF(Met) polymorphism. Importantly, 
      desipramine but not fluoxetine has antidepressant effects on BDNF(+/Met) mice, 
      suggesting that specific classes of antidepressant may be a more effective 
      treatment option for depressive symptoms in humans with this genetic variant 
      BDNF.
FAU - Yu, Hui
AU  - Yu H
AD  - Department of Neurobiology, Shandong University, Jinan, Shandong, Peoples 
      Republic of China.
FAU - Wang, Dong-Dong
AU  - Wang DD
FAU - Wang, Yue
AU  - Wang Y
FAU - Liu, Ting
AU  - Liu T
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  - R01 NS052819/NS/NINDS NIH HHS/United States
GR  - NS052819/NS/NINDS NIH HHS/United States
GR  - R01 NS052819-06/NS/NINDS NIH HHS/United States
GR  - P50 MH079513-04/MH/NIMH NIH HHS/United States
GR  - P50 MH079513/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 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Elk3 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Slc6a4 protein, mouse)
RN  - 0 (Sweetening Agents)
RN  - 57-50-1 (Sucrose)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Analysis of Variance
MH  - Animals
MH  - Antidepressive Agents/*therapeutic use
MH  - Brain/metabolism/ultrastructure
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Circadian Rhythm/genetics/physiology
MH  - Corticosterone/blood
MH  - Corticotropin-Releasing Hormone/blood
MH  - Dendritic Spines/metabolism/ultrastructure
MH  - Depression/*drug therapy/etiology
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay/methods
MH  - Exploratory Behavior/drug effects/physiology
MH  - Food Preferences/physiology
MH  - Gene Expression Regulation/genetics
MH  - Male
MH  - Maze Learning/drug effects/physiology
MH  - Methionine/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Proto-Oncogene Proteins c-ets/genetics/metabolism
MH  - Pyramidal Cells/metabolism/ultrastructure
MH  - RNA, Messenger/metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Silver Staining
MH  - Stress, Psychological/complications/drug therapy/*genetics/pathology
MH  - Sucrose/administration & dosage
MH  - Sweetening Agents/administration & dosage
MH  - Swimming/psychology
MH  - Valine/*genetics
PMC - PMC3319323
MID - NIHMS366157
EDAT- 2012/03/24 06:00
MHDA- 2012/05/19 06:00
PMCR- 2012/09/21
CRDT- 2012/03/24 06:00
PHST- 2012/03/24 06:00 [entrez]
PHST- 2012/03/24 06:00 [pubmed]
PHST- 2012/05/19 06:00 [medline]
PHST- 2012/09/21 00:00 [pmc-release]
AID - 32/12/4092 [pii]
AID - 3762871 [pii]
AID - 10.1523/JNEUROSCI.5048-11.2012 [doi]
PST - ppublish
SO  - J Neurosci. 2012 Mar 21;32(12):4092-101. doi: 10.1523/JNEUROSCI.5048-11.2012.