PMID- 24852757
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  - Effects of prenatal cocaine exposure on social development in mice.
PG  - 338-46
LID - 10.1159/000360524 [doi]
AB  - Prenatal cocaine exposure (PCE) in humans and animals has been shown to impair 
      social development. Molecules that mediate synaptic plasticity and learning in 
      the medial prefrontal cortex (mPFC), specifically brain-derived neurotrophic 
      factor (BDNF) and its downstream signaling molecule, early growth response 
      protein 1 (egr1), have been shown to affect the regulation of social interactions 
      (SI). In this study we determined the effects of PCE on SI and the corresponding 
      ultrasonic vocalizations (USVs) in developing mice. Furthermore, we studied the 
      PCE-induced changes in the constitutive expression of BDNF, egr1 and their 
      transcriptional regulators in the mPFC as a possible molecular mechanism 
      mediating the altered SI. In prenatal cocaine-exposed (PCOC) mice we identified 
      increased SI and USV production at postnatal day (PD) 25, and increased SI but 
      not USVs at PD35. By PD45 the expression of both social behaviors normalized in 
      PCOC mice. At the molecular level, we found increased BDNF exon IV and egr1 mRNA 
      in the mPFC of PCOC mice at PD30 that normalized by PD45. This was concurrent 
      with increased EGR1 protein in the mPFC of PCOC mice at PD30, suggesting a role 
      of egr1 in the enhanced SI observed in juvenile PCOC mice. Additionally, by 
      measuring the association of acetylation of histone 3 at lysine residues 9 and 14 
      (acH3K9,14) and MeCP2 at the promoters of BDNF exons I and IV and egr1, our 
      results provide evidence of promoter-specific alterations in the mPFC of PCOC 
      juvenile mice, with increased association of acH3K9,14 only at the BDNF exon IV 
      promoter. These results identify a potential PCE-induced molecular alteration as 
      the underlying neurobiological mechanism mediating the altered social development 
      in juvenile mice.
CI  - (c) 2014 S. Karger AG, Basel.
FAU - Kabir, Zeeba D
AU  - Kabir ZD
AD  - Department of Pediatrics, Division of Pediatric Neurology, Weill Cornell Medical 
      College, New York, N.Y., USA.
FAU - Kennedy, Bruce
AU  - Kennedy B
FAU - Katzman, Aaron
AU  - Katzman A
FAU - Lahvis, Garet P
AU  - Lahvis GP
FAU - Kosofsky, Barry E
AU  - Kosofsky BE
LA  - eng
GR  - R01 DA017905/DA/NIDA NIH HHS/United States
GR  - DA017905/DA/NIDA NIH HHS/United States
GR  - DA00354/DA/NIDA NIH HHS/United States
GR  - R01 DA008648/DA/NIDA NIH HHS/United States
GR  - DA02254-05/DA/NIDA NIH HHS/United States
GR  - K02 DA000354/DA/NIDA NIH HHS/United States
GR  - T32 DA007097/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140513
PL  - Switzerland
TA  - Dev Neurosci
JT  - Developmental neuroscience
JID - 7809375
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - Aging/psychology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cocaine/*adverse effects
MH  - Early Growth Response Protein 1/metabolism
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Interpersonal Relations
MH  - Male
MH  - Mice
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*psychology
MH  - *Social Behavior
MH  - Vocalization, Animal/drug effects
PMC - PMC4125482
MID - NIHMS573672
COIS- Disclosure The authors report no financial interests or conflicts of interest.
EDAT- 2014/05/24 06:00
MHDA- 2015/04/18 06:00
PMCR- 2015/05/13
CRDT- 2014/05/24 06:00
PHST- 2013/12/30 00:00 [received]
PHST- 2014/02/10 00:00 [accepted]
PHST- 2014/05/24 06:00 [entrez]
PHST- 2014/05/24 06:00 [pubmed]
PHST- 2015/04/18 06:00 [medline]
PHST- 2015/05/13 00:00 [pmc-release]
AID - 000360524 [pii]
AID - 10.1159/000360524 [doi]
PST - ppublish
SO  - Dev Neurosci. 2014;36(3-4):338-46. doi: 10.1159/000360524. Epub 2014 May 13.