PMID- 26756904
OWN - NLM
STAT- MEDLINE
DCOM- 20161017
LR  - 20240213
IS  - 2158-3188 (Electronic)
IS  - 2158-3188 (Linking)
VI  - 6
IP  - 1
DP  - 2016 Jan 12
TI  - Behavioral and molecular neuroepigenetic alterations in prenatally stressed mice: 
      relevance for the study of chromatin remodeling properties of antipsychotic 
      drugs.
PG  - e711
LID - 10.1038/tp.2015.191 [doi]
AB  - We have recently reported that mice born from dams stressed during pregnancy (PRS 
      mice), in adulthood, have behavioral deficits reminiscent of behaviors observed 
      in schizophrenia (SZ) and bipolar (BP) disorder patients. Furthermore, we have 
      shown that the frontal cortex (FC) and hippocampus of adult PRS mice, like that 
      of postmortem chronic SZ patients, are characterized by increases in 
      DNA-methyltransferase 1 (DNMT1), ten-eleven methylcytosine dioxygenase 1 (TET1) 
      and exhibit an enrichment of 5-methylcytosine (5MC) and 5-hydroxymethylcytosine 
      (5HMC) at neocortical GABAergic and glutamatergic gene promoters. Here, we show 
      that the behavioral deficits and the increased 5MC and 5HMC at glutamic acid 
      decarboxylase 67 (Gad1), reelin (Reln) and brain-derived neurotrophic factor 
      (Bdnf) promoters and the reduced expression of the messenger RNAs (mRNAs) and 
      proteins corresponding to these genes in FC of adult PRS mice is reversed by 
      treatment with clozapine (5 mg kg(-1) twice a day for 5 days) but not by 
      haloperidol (1 mg kg(-1) twice a day for 5 days). Interestingly, clozapine had no 
      effect on either the behavior, promoter methylation or the expression of these 
      mRNAs and proteins when administered to offspring of nonstressed pregnant mice. 
      Clozapine, but not haloperidol, reduced the elevated levels of DNMT1 and TET1, as 
      well as the elevated levels of DNMT1 binding to Gad1, Reln and Bdnf promoters in 
      PRS mice suggesting that clozapine, unlike haloperidol, may limit DNA methylation 
      by interfering with DNA methylation dynamics. We conclude that the PRS mouse 
      model may be useful preclinically in screening for the potential efficacy of 
      antipsychotic drugs acting on altered epigenetic mechanisms. Furthermore, PRS 
      mice may be invaluable for understanding the etiopathogenesis of SZ and BP 
      disorder and for predicting treatment responses at early stages of the illness 
      allowing for early detection and remedial intervention.
FAU - Dong, E
AU  - Dong E
AD  - The Psychiatric Institute, Department of Psychiatry, College of Medicine, 
      University of Illinois at Chicago, Chicago, IL, USA.
FAU - Tueting, P
AU  - Tueting P
AD  - The Psychiatric Institute, Department of Psychiatry, College of Medicine, 
      University of Illinois at Chicago, Chicago, IL, USA.
FAU - Matrisciano, F
AU  - Matrisciano F
AD  - The Psychiatric Institute, Department of Psychiatry, College of Medicine, 
      University of Illinois at Chicago, Chicago, IL, USA.
FAU - Grayson, D R
AU  - Grayson DR
AD  - The Psychiatric Institute, Department of Psychiatry, College of Medicine, 
      University of Illinois at Chicago, Chicago, IL, USA.
FAU - Guidotti, A
AU  - Guidotti A
AD  - The Psychiatric Institute, Department of Psychiatry, College of Medicine, 
      University of Illinois at Chicago, Chicago, IL, USA.
LA  - eng
GR  - R01 MH093348/MH/NIMH NIH HHS/United States
GR  - R01 MH101043/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160112
PL  - United States
TA  - Transl Psychiatry
JT  - Translational psychiatry
JID - 101562664
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Reelin Protein)
RN  - EC 3.4.21.- (Reln protein, mouse)
RN  - J60AR2IKIC (Clozapine)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*pharmacology
MH  - Behavior, Animal/*drug effects/physiology
MH  - Blotting, Western
MH  - Brain/*drug effects/physiopathology
MH  - Chromatin Assembly and Disassembly/*drug effects/physiology
MH  - Clozapine/pharmacology
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic/drug effects
MH  - Female
MH  - Mice
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*physiopathology
MH  - Real-Time Polymerase Chain Reaction
MH  - Reelin Protein
MH  - Stress, Psychological/*physiopathology
PMC - PMC5068871
EDAT- 2016/01/13 06:00
MHDA- 2016/10/19 06:00
PMCR- 2016/01/01
CRDT- 2016/01/13 06:00
PHST- 2015/06/22 00:00 [received]
PHST- 2015/09/29 00:00 [revised]
PHST- 2015/10/21 00:00 [accepted]
PHST- 2016/01/13 06:00 [entrez]
PHST- 2016/01/13 06:00 [pubmed]
PHST- 2016/10/19 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - tp2015191 [pii]
AID - 10.1038/tp.2015.191 [doi]
PST - epublish
SO  - Transl Psychiatry. 2016 Jan 12;6(1):e711. doi: 10.1038/tp.2015.191.