PMID- 22572518
OWN - NLM
STAT- MEDLINE
DCOM- 20130222
LR  - 20211021
IS  - 1421-9859 (Electronic)
IS  - 0378-5866 (Linking)
VI  - 34
IP  - 2-3
DP  - 2012
TI  - Brain-derived neurotrophic factor genotype impacts the prenatal cocaine-induced 
      mouse phenotype.
PG  - 184-97
AB  - Prenatal cocaine exposure leads to persistent alterations in the growth factor 
      brain-derived neurotrophic factor (BDNF), particularly in the medial prefrontal 
      cortex (mPFC) and hippocampus, brain regions important in cognitive functioning. 
      BDNF plays an important role in the strengthening of existing synaptic 
      connections as well as in the formation of new contacts during learning. A single 
      nucleotide polymorphism in the BDNF gene (Val66Met), leading to a Met 
      substitution for Val at codon 66 in the prodomain, is common in human 
      populations, with an allele frequency of 20-30% in Caucasians. To study the 
      interaction between prenatal cocaine exposure and BDNF, we have utilized a line 
      of BDNF Val66Met transgenic mice on a Swiss Webster background in which BDNF(Met) 
      is endogenously expressed. Examination of baseline levels of mature BDNF protein 
      in the mPFC of prenatally cocaine-treated wild-type (Val66Val) and Val66Met mice 
      revealed significantly lower levels compared to prenatally saline-treated mice. 
      In contrast, in the hippocampus of prenatally saline- and cocaine-treated adult 
      Val66Met mice, there were significantly lower levels of mature BDNF protein 
      compared to Val66Val mice. In extinction of a conditioned fear, we found that 
      prenatally cocaine-treated Val66Met mice had a deficit in recall of extinction. 
      Examination of mature BDNF protein levels immediately after the test for 
      extinction recall revealed lower levels in the mPFC of prenatally cocaine-treated 
      Val66Met mice compared to saline-treated mice. However, 2 h after the extinction 
      test, there was increased BDNF exons I, IV, and IX mRNA expression in the 
      prelimbic cortex of the mPFC in the prenatally cocaine-treated BDNF Val66Met mice 
      compared to prenatally saline-treated mice. Taken together, our results suggest 
      the possibility that prenatal cocaine-induced constitutive alterations in BDNF 
      mRNA and protein expression in the mPFC differentially poises animals for 
      alterations in behaviorally induced gene activation, which are interactive with 
      BDNF genotype and differentially impact those behaviors. Such findings in our 
      prenatal cocaine mouse model suggest a gene X environment interaction of 
      potential clinical relevance.
CI  - Copyright (c) 2012 S. Karger AG, Basel.
FAU - Kabir, Zeeba D
AU  - Kabir ZD
AD  - Division of Pediatric Neurology, Department of Pediatrics, Weill Cornell Medical 
      College, New York, NY 10021, USA.
FAU - Lourenco, Frederico
AU  - Lourenco F
FAU - Byrne, Maureen E
AU  - Byrne ME
FAU - Katzman, Aaron
AU  - Katzman A
FAU - Lee, Francis
AU  - Lee F
FAU - Rajadhyaksha, Anjali M
AU  - Rajadhyaksha AM
FAU - Kosofsky, Barry E
AU  - Kosofsky BE
LA  - eng
GR  - F31 DA032169/DA/NIDA NIH HHS/United States
GR  - R01 DA029122/DA/NIDA NIH HHS/United States
GR  - R01 DA08648/DA/NIDA NIH HHS/United States
GR  - K02 DA00354/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120508
PL  - Switzerland
TA  - Dev Neurosci
JT  - Developmental neuroscience
JID - 7809375
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Animals
MH  - Anxiety/genetics/metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cocaine/*pharmacology
MH  - Conditioning, Psychological/drug effects
MH  - Dopamine Uptake Inhibitors/*pharmacology
MH  - Extinction, Psychological/drug effects
MH  - Fear/drug effects
MH  - Female
MH  - Gene Frequency/drug effects
MH  - Genotype
MH  - Hippocampus/*drug effects/metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Phenotype
MH  - Polymorphism, Single Nucleotide/drug effects
MH  - Prefrontal Cortex/*drug effects/metabolism
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*genetics/metabolism
EDAT- 2012/05/11 06:00
MHDA- 2013/02/23 06:00
CRDT- 2012/05/11 06:00
PHST- 2011/12/09 00:00 [received]
PHST- 2012/03/05 00:00 [accepted]
PHST- 2012/05/11 06:00 [entrez]
PHST- 2012/05/11 06:00 [pubmed]
PHST- 2013/02/23 06:00 [medline]
AID - 000337712 [pii]
AID - 10.1159/000337712 [doi]
PST - ppublish
SO  - Dev Neurosci. 2012;34(2-3):184-97. doi: 10.1159/000337712. Epub 2012 May 8.