PMID- 24358339
OWN - NLM
STAT- MEDLINE
DCOM- 20140916
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 12
DP  - 2013
TI  - Molecular mechanisms mediating a deficit in recall of fear extinction in adult 
      mice exposed to cocaine in utero.
PG  - e84165
LID - 10.1371/journal.pone.0084165 [doi]
LID - e84165
AB  - Prenatal cocaine exposure has been shown to alter cognitive processes of exposed 
      individuals, presumed to be a result of long-lasting molecular alterations in the 
      brain. In adult prenatal cocaine exposed (PCOC) mice we have identified a deficit 
      in recall of fear extinction, a behavior that is dependent on the medial 
      prefrontal cortex (mPFC) and the hippocampus. While we observed no change in the 
      constitutive expression of brain derived neurotrophic factor (BDNF) protein and 
      mRNA in the mPFC and hippocampus of adult PCOC mice, we observed blunted BDNF 
      signaling in the mPFC of adult PCOC mice after fear extinction compared to the 
      control animals. Specifically, during the consolidation phase of the extinction 
      memory, we observed a decrease in BDNF protein and it's phospho-TrkB receptor 
      expression. Interestingly, at this same time point there was a significant 
      increase in total Bdnf mRNA levels in the mPFC of PCOC mice as compared with 
      controls. In the Bdnf gene, we identified decreased constitutive binding of the 
      transcription factors, MeCP2 and P-CREB at the promoters of Bdnf exons I and IV 
      in the mPFC of PCOC mice, that unlike control mice remained unchanged when 
      measured during the behavior. Finally, bilateral infusion of recombinant BDNF 
      protein into the infralimbic subdivision of the mPFC during the consolidation 
      phase of the extinction memory rescued the behavioral deficit in PCOC mice. In 
      conclusion, these findings extend our knowledge of the neurobiologic impact of 
      prenatal cocaine exposure on the mPFC of mice, which may lead to improved 
      clinical recognition and treatment of exposed individuals.
FAU - Kabir, Zeeba D
AU  - Kabir ZD
AD  - Division of Pediatric Neurology, Department of Pediatrics, Weill Cornell Medical 
      College, New York, New York, United States of America ; Brain and Mind Institute, 
      Weill Cornell Medical College, New York, New York, United States of America.
FAU - Katzman, Aaron C
AU  - Katzman AC
AD  - Department of Psychiatry, University of Iowa, Iowa City, Iowa, United States of 
      America.
FAU - Kosofsky, Barry E
AU  - Kosofsky BE
AD  - Division of Pediatric Neurology, Department of Pediatrics, Weill Cornell Medical 
      College, New York, New York, United States of America ; Brain and Mind Institute, 
      Weill Cornell Medical College, New York, New York, United States of America.
LA  - eng
GR  - K02 DA000354/DA/NIDA NIH HHS/United States
GR  - R01 DA008648/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
PT  - Research Support, Non-U.S. Gov't
DEP - 20131217
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Alternative Splicing
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism/pharmacology
MH  - Cocaine/*pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Exons
MH  - Extinction, Psychological/*drug effects
MH  - Fear/*drug effects
MH  - Female
MH  - Hippocampus/metabolism/physiopathology
MH  - Male
MH  - Memory
MH  - Mental Recall/*drug effects
MH  - Methyl-CpG-Binding Protein 2/metabolism
MH  - Mice
MH  - Prefrontal Cortex/metabolism/physiopathology
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA, Messenger/genetics
MH  - Receptor, trkB/metabolism
PMC - PMC3866142
COIS- Competing Interests: The authors have declared no competing interests exist.
EDAT- 2013/12/21 06:00
MHDA- 2014/09/17 06:00
PMCR- 2013/12/17
CRDT- 2013/12/21 06:00
PHST- 2013/10/29 00:00 [received]
PHST- 2013/11/20 00:00 [accepted]
PHST- 2013/12/21 06:00 [entrez]
PHST- 2013/12/21 06:00 [pubmed]
PHST- 2014/09/17 06:00 [medline]
PHST- 2013/12/17 00:00 [pmc-release]
AID - PONE-D-13-44072 [pii]
AID - 10.1371/journal.pone.0084165 [doi]
PST - epublish
SO  - PLoS One. 2013 Dec 17;8(12):e84165. doi: 10.1371/journal.pone.0084165. 
      eCollection 2013.