PMID- 25444166
OWN - NLM
STAT- MEDLINE
DCOM- 20151130
LR  - 20181113
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 77
IP  - 6
DP  - 2015 Mar 15
TI  - Brain-derived neurotrophic factor epigenetic modifications associated with 
      schizophrenia-like phenotype induced by prenatal stress in mice.
PG  - 589-96
LID - S0006-3223(14)00634-9 [pii]
LID - 10.1016/j.biopsych.2014.08.012 [doi]
AB  - BACKGROUND: Prenatal stress (PRS) is considered a risk factor for several 
      neurodevelopmental disorders including schizophrenia (SZ). An animal model 
      involving restraint stress of pregnant mice suggests that PRS induces epigenetic 
      changes in specific GABAergic and glutamatergic genes likely to be implicated in 
      SZ, including the gene for brain-derived neurotrophic factor (BDNF). METHODS: 
      Studying adult offspring of pregnant mice subjected to PRS, we explored the 
      long-term effects of PRS on behavior and on the expression of key chromatin 
      remodeling factors including DNA methyltransferase 1, ten-eleven-translocation 
      hydroxylases, methyl CpG binding protein 2, histone deacetylases, and histone 
      methyltransferases and demethylase in the frontal cortex and hippocampus. We also 
      measured the expression of BDNF. RESULTS: Adult PRS offspring demonstrate 
      behavioral abnormalities suggestive of SZ and molecular changes similar to 
      changes seen in postmortem brains of patients with SZ. This includes a 
      significant increase in DNA methyltransferase 1 and ten-eleven-translocation 
      hydroxylase 1 in the frontal cortex and hippocampus but not in cerebellum; no 
      changes in histone deacetylases, histone methyltransferases and demethylases, or 
      methyl CpG binding protein 2, and a significant decrease in Bdnf messenger RNA 
      variants. The decrease of the corresponding Bdnf transcript level was accompanied 
      by an enrichment of 5-methylcytosine and 5-hydroxymethylcytosine at Bdnf gene 
      regulatory regions. In addition, the expression of Bdnf transcripts (IV and IX) 
      correlated positively with social approach in both PRS mice and nonstressed mice. 
      CONCLUSIONS: Because patients with psychosis and PRS mice show similar epigenetic 
      signature, PRS mice may be a suitable model for understanding the behavioral and 
      molecular epigenetic changes observed in patients with SZ.
CI  - Copyright (c) 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Dong, Erbo
AU  - Dong E
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois. Electronic address: 
      Edong@psych.uic.edu.
FAU - Dzitoyeva, Svetlana G
AU  - Dzitoyeva SG
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Matrisciano, Francesco
AU  - Matrisciano F
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Tueting, Patricia
AU  - Tueting P
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Grayson, Dennis R
AU  - Grayson DR
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois.
FAU - Guidotti, Alessandro
AU  - Guidotti A
AD  - Psychiatric Institute, Department of Psychiatry, College of Medicine, University 
      of Illinois at Chicago, Chicago, Illinois.
LA  - eng
GR  - R01 MH093348/MH/NIMH NIH HHS/United States
GR  - R01 MH101043/MH/NIMH NIH HHS/United States
GR  - R01MH101043/MH/NIMH NIH HHS/United States
GR  - R01MN093348/MN/OMHHE CDC HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140827
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chromatin)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Chromatin/metabolism
MH  - DNA Methylation
MH  - Disease Models, Animal
MH  - *Epigenesis, Genetic
MH  - Female
MH  - Male
MH  - Mice
MH  - Motor Activity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Restraint, Physical
MH  - Schizophrenia/*genetics/physiopathology
MH  - Social Behavior
MH  - Stress, Psychological/*genetics/physiopathology
PMC - PMC4333020
MID - NIHMS649608
OTO - NOTNLM
OT  - BDNF
OT  - DNA methylation
OT  - DNMT
OT  - Prenatal stress
OT  - Schizophrenia
OT  - TET
COIS- Conflict of Interest None of the authors have any disclosures to make about 
      actual or potential financial or other conflicts of interests.
EDAT- 2014/12/03 06:00
MHDA- 2015/12/15 06:00
PMCR- 2015/03/15
CRDT- 2014/12/03 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2014/07/31 00:00 [revised]
PHST- 2014/08/19 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
PHST- 2015/03/15 00:00 [pmc-release]
AID - S0006-3223(14)00634-9 [pii]
AID - 10.1016/j.biopsych.2014.08.012 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2015 Mar 15;77(6):589-96. doi: 10.1016/j.biopsych.2014.08.012. 
      Epub 2014 Aug 27.