PMID- 24992985
OWN - NLM
STAT- MEDLINE
DCOM- 20150417
LR  - 20211021
IS  - 1421-9859 (Electronic)
IS  - 0378-5866 (Print)
IS  - 0378-5866 (Linking)
VI  - 36
IP  - 3-4
DP  - 2014
TI  - BDNF modulates contextual fear learning during adolescence.
PG  - 269-76
LID - 10.1159/000358824 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) is a growth factor that plays key roles 
      in regulating higher-order emotional and cognitive processes including fear 
      learning and memory. A common single-nucleotide polymorphism (SNP) has been 
      identified in the human BDNF gene (BDNF Val66Met) that leads to decreased BDNF 
      secretion and impairments in specific forms of fear learning in adult humans and 
      genetically modified mice containing this SNP. As the emergence of anxiety and 
      other fear-related disorders peaks during adolescence, we sought to better 
      understand the impact of this BDNF SNP on fear learning during the transition 
      through adolescence in BDNF Val66Met knock-in mice. Previously, we have shown 
      that contextual fear expression is temporarily suppressed in wild-type mice 
      during a distinct period in adolescence, but re-emerges at later, postadolescent 
      ages. Until recently, it was unclear whether BDNF-TrkB signaling is involved in 
      the modulation of hippocampal-dependent contextual fear learning and memory 
      during this adolescent period. Here we show that in BDNF Val66Met mice, the 
      presence of the Met allele does not alter contextual fear expression during 
      adolescence, but when previously conditioned BDNF(Met/Met) mice are tested in 
      adulthood, they fail to display the delayed expression of contextual fear 
      compared to wild-type BDNF(Val/Val) controls, indicating that the Met allele may 
      permanently alter hippocampal function, leading to persistent functioning that is 
      indistinguishable from the adolescent state. Conversely, truncated TrkB receptor 
      (TrkB.T1)-deficient (TrkB.T1(-/-)) mice, a genetic mouse model with increased 
      BDNF-TrkB signaling through full-length TrkB receptors, exhibit an accelerated 
      expression of contextual fear during adolescence compared to wild-type controls. 
      Our results point to a critical function for BDNF-TrkB signaling in fear 
      regulation in vivo, particularly during a potentially sensitive period in 
      adolescence.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Dincheva, Iva
AU  - Dincheva I
AD  - Department of Psychiatry, Weill Cornell Medical College of Cornell University, 
      New York, N.Y., USA.
FAU - Pattwell, Siobhan S
AU  - Pattwell SS
FAU - Tessarollo, Lino
AU  - Tessarollo L
FAU - Bath, Kevin G
AU  - Bath KG
FAU - Lee, Francis S
AU  - Lee FS
LA  - eng
GR  - MH079513/MH/NIMH NIH HHS/United States
GR  - P50 MH079513/MH/NIMH NIH HHS/United States
GR  - HD055177/HD/NICHD NIH HHS/United States
GR  - R01 NS052819/NS/NINDS NIH HHS/United States
GR  - NS052819/NS/NINDS NIH HHS/United States
GR  - T32 HD055177/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140701
PL  - Switzerland
TA  - Dev Neurosci
JT  - Developmental neuroscience
JID - 7809375
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Aging/psychology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/*physiology
MH  - Fear/*psychology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/physiology
MH  - Hippocampus/physiology
MH  - Learning/*physiology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Polymorphism, Single Nucleotide
MH  - Receptor, trkB/genetics
PMC - PMC4150737
MID - NIHMS571254
EDAT- 2014/07/06 06:00
MHDA- 2015/04/18 06:00
PMCR- 2015/07/01
CRDT- 2014/07/05 06:00
PHST- 2013/12/03 00:00 [received]
PHST- 2014/01/17 00:00 [accepted]
PHST- 2014/07/05 06:00 [entrez]
PHST- 2014/07/06 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
PHST- 2015/07/01 00:00 [pmc-release]
AID - 000358824 [pii]
AID - 10.1159/000358824 [doi]
PST - ppublish
SO  - Dev Neurosci. 2014;36(3-4):269-76. doi: 10.1159/000358824. Epub 2014 Jul 1.