PMID- 18497103
OWN - NLM
STAT- MEDLINE
DCOM- 20080807
LR  - 20211020
IS  - 1528-2511 (Print)
IS  - 1528-2511 (Linking)
VI  - 289
DP  - 2008
TI  - Impact of genetic variant BDNF (Val66Met) on brain structure and function.
PG  - 180-8; discussion 188-95
AB  - A common single-nucleotide polymorphism in the human brain-derived neurotrophic 
      factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 
      (Val66Met), is associated with alterations in brain anatomy and memory, but its 
      relevance to clinical disorders is unclear. We generated a variant BDNF mouse 
      (BDNF(MET/Met)) that reproduces the phenotypic hallmarks in humans with the 
      variant allele. Variant BDNF(Met) was expressed in brain at normal levels, but 
      its secretion from neurons was defective. In this context, the BDNF(Met/Met) 
      mouse represents a unique model that directly links altered activity-dependent 
      release of BDNF to a defined set of in vivo consequences. Our subsequent analyses 
      of these mice elucidated a phenotype that had not been established in human 
      carriers: increased anxiety. When placed in conflict settings, BDNF(Met/Met) mice 
      display increased anxiety-related behaviours that were not normalized by the 
      antidepressant, fluoxetine. A genetic variant BDNF may thus play a key role in 
      genetic predispositions to anxiety and depressive disorders.
FAU - Chen, Zhe-Yu
AU  - Chen ZY
AD  - Department of Psychiatry, Weill Medical College of Cornell University, New York, 
      NY 10021, USA.
FAU - Bath, Kevin
AU  - Bath K
FAU - McEwen, Bruce
AU  - McEwen B
FAU - Hempstead, Barbara
AU  - Hempstead B
FAU - Lee, Francis
AU  - Lee F
LA  - eng
GR  - P50 MH079513-01A10001/MH/NIMH NIH HHS/United States
GR  - R01 NS052819/NS/NINDS NIH HHS/United States
GR  - R01 NS052819-04/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Review
PL  - England
TA  - Novartis Found Symp
JT  - Novartis Foundation symposium
JID - 9807767
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Growth Substances)
RN  - AE28F7PNPL (Methionine)
RN  - HG18B9YRS7 (Valine)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Anxiety Disorders/*genetics
MH  - Brain/*anatomy & histology/*physiology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Depressive Disorder/*genetics
MH  - Genetic Predisposition to Disease
MH  - *Genetic Variation
MH  - Growth Substances/physiology
MH  - Humans
MH  - Mental Disorders/*genetics
MH  - Methionine
MH  - Mice
MH  - Mice, Transgenic
MH  - *Polymorphism, Single Nucleotide
MH  - Psychotic Disorders/genetics
MH  - Valine
PMC - PMC2735856
MID - NIHMS105402
EDAT- 2008/05/24 09:00
MHDA- 2008/08/08 09:00
PMCR- 2009/09/01
CRDT- 2008/05/24 09:00
PHST- 2008/05/24 09:00 [pubmed]
PHST- 2008/08/08 09:00 [medline]
PHST- 2008/05/24 09:00 [entrez]
PHST- 2009/09/01 00:00 [pmc-release]
AID - 10.1002/9780470751251.ch14 [doi]
PST - ppublish
SO  - Novartis Found Symp. 2008;289:180-8; discussion 188-95. doi: 
      10.1002/9780470751251.ch14.