PMID- 21306736
OWN - NLM
STAT- MEDLINE
DCOM- 20110830
LR  - 20230113
IS  - 1879-1379 (Electronic)
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 45
IP  - 7
DP  - 2011 Jul
TI  - Epigenetic modification of hippocampal Bdnf DNA in adult rats in an animal model 
      of post-traumatic stress disorder.
PG  - 919-26
LID - 10.1016/j.jpsychires.2011.01.013 [doi]
AB  - Epigenetic alterations of the brain-derived neurotrophic factor (Bdnf) gene have 
      been linked with memory, stress, and neuropsychiatric disorders. Here we examined 
      whether there was a link between an established rat model of post-traumatic 
      stress disorder (PTSD) and Bdnf DNA methylation. Adult male Sprague-Dawley rats 
      were given psychosocial stress composed of two acute cat exposures in conjunction 
      with 31 days of daily social instability. These manipulations have been shown 
      previously to produce physiological and behavioral sequelae in rats that are 
      comparable to symptoms observed in traumatized people with PTSD. We then assessed 
      Bdnf DNA methylation patterns (at exon IV) and gene expression. We have found 
      here that the psychosocial stress regimen significantly increased Bdnf DNA 
      methylation in the dorsal hippocampus, with the most robust hypermethylation 
      detected in the dorsal CA1 subregion. Conversely, the psychosocial stress regimen 
      significantly decreased methylation in the ventral hippocampus (CA3). No changes 
      in Bdnf DNA methylation were detected in the medial prefrontal cortex or 
      basolateral amygdala. In addition, there were decreased levels of Bdnf mRNA in 
      both the dorsal and ventral CA1. These results provide evidence that traumatic 
      stress occurring in adulthood can induce CNS gene methylation, and specifically, 
      support the hypothesis that epigenetic marking of the Bdnf gene may underlie 
      hippocampal dysfunction in response to traumatic stress. Furthermore, this work 
      provides support for the speculative notion that altered hippocampal Bdnf DNA 
      methylation is a cellular mechanism underlying the persistent cognitive deficits 
      which are prominent features of the pathophysiology of PTSD.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Roth, Tania L
AU  - Roth TL
AD  - Department of Psychology, University of Delaware, Newark, DE 19716, USA. 
      troth@psych.udel.edu
FAU - Zoladz, Phillip R
AU  - Zoladz PR
FAU - Sweatt, J David
AU  - Sweatt JD
FAU - Diamond, David M
AU  - Diamond DM
LA  - eng
GR  - R01 MH057014/MH/NIMH NIH HHS/United States
GR  - R01 MH057014-04A1/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110209
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - DNA Methylation/*genetics
MH  - Epigenesis, Genetic/*genetics
MH  - Gene Expression/genetics
MH  - Hippocampus/*metabolism/physiopathology
MH  - Male
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Social Environment
MH  - Stress Disorders, Post-Traumatic/*genetics/physiopathology
MH  - Stress, Psychological/complications
PMC - PMC3335738
MID - NIHMS267098
EDAT- 2011/02/11 06:00
MHDA- 2011/08/31 06:00
PMCR- 2012/07/01
CRDT- 2011/02/11 06:00
PHST- 2010/08/26 00:00 [received]
PHST- 2011/11/11 00:00 [revised]
PHST- 2011/11/13 00:00 [accepted]
PHST- 2011/02/11 06:00 [entrez]
PHST- 2011/02/11 06:00 [pubmed]
PHST- 2011/08/31 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - S0022-3956(11)00014-8 [pii]
AID - 10.1016/j.jpsychires.2011.01.013 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2011 Jul;45(7):919-26. doi: 10.1016/j.jpsychires.2011.01.013. 
      Epub 2011 Feb 9.