PMID- 16501568
OWN - NLM
STAT- MEDLINE
DCOM- 20060608
LR  - 20230817
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 9
IP  - 4
DP  - 2006 Apr
TI  - Sustained hippocampal chromatin regulation in a mouse model of depression and 
      antidepressant action.
PG  - 519-25
AB  - To better understand the molecular mechanisms of depression and antidepressant 
      action, we administered chronic social defeat stress followed by chronic 
      imipramine (a tricyclic antidepressant) to mice and studied adaptations at the 
      levels of gene expression and chromatin remodeling of five brain-derived 
      neurotrophic factor (Bdnf) splice variant mRNAs (I-V) and their unique promoters 
      in the hippocampus. Defeat stress induced lasting downregulation of Bdnf 
      transcripts III and IV and robustly increased repressive histone methylation at 
      their corresponding promoters. Chronic imipramine reversed this downregulation 
      and increased histone acetylation at these promoters. This hyperacetylation by 
      chronic imipramine was associated with a selective downregulation of histone 
      deacetylase (Hdac) 5. Furthermore, viral-mediated HDAC5 overexpression in the 
      hippocampus blocked imipramine's ability to reverse depression-like behavior. 
      These experiments underscore an important role for histone remodeling in the 
      pathophysiology and treatment of depression and highlight the therapeutic 
      potential for histone methylation and deacetylation inhibitors in depression.
FAU - Tsankova, Nadia M
AU  - Tsankova NM
AD  - The University of Texas Southwestern Medical Center, Department of Psychiatry and 
      Center for Basic Neuroscience, 5323 Harry Hines Boulevard, Dallas, Texas 
      75390-9070, USA.
FAU - Berton, Olivier
AU  - Berton O
FAU - Renthal, William
AU  - Renthal W
FAU - Kumar, Arvind
AU  - Kumar A
FAU - Neve, Rachel L
AU  - Neve RL
FAU - Nestler, Eric J
AU  - Nestler EJ
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060226
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Antidepressive Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chromatin)
RN  - 0 (Histones)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
CIN - Nat Neurosci. 2006 Apr;9(4):465-6. PMID: 16568101
MH  - Acetylation
MH  - Animals
MH  - Antidepressive Agents/*pharmacology/therapeutic use
MH  - Behavior, Animal/physiology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Chromatin/*metabolism
MH  - Depression/drug therapy/*physiopathology
MH  - Disease Models, Animal
MH  - Hippocampus/cytology/*drug effects/*physiology
MH  - Histones/metabolism
MH  - Imipramine/pharmacology/therapeutic use
MH  - Male
MH  - Methylation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Stress, Psychological/metabolism
EDAT- 2006/02/28 09:00
MHDA- 2006/06/09 09:00
CRDT- 2006/02/28 09:00
PHST- 2006/01/03 00:00 [received]
PHST- 2006/01/31 00:00 [accepted]
PHST- 2006/02/28 09:00 [pubmed]
PHST- 2006/06/09 09:00 [medline]
PHST- 2006/02/28 09:00 [entrez]
AID - nn1659 [pii]
AID - 10.1038/nn1659 [doi]
PST - ppublish
SO  - Nat Neurosci. 2006 Apr;9(4):519-25. doi: 10.1038/nn1659. Epub 2006 Feb 26.