PMID- 22592058
OWN - NLM
STAT- MEDLINE
DCOM- 20130206
LR  - 20220129
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 72
IP  - 7
DP  - 2012 Oct 1
TI  - Deletion of CREB-regulated transcription coactivator 1 induces pathological 
      aggression, depression-related behaviors, and neuroplasticity genes dysregulation 
      in mice.
PG  - 528-36
LID - 10.1016/j.biopsych.2012.04.011 [doi]
AB  - BACKGROUND: Mood disorders are polygenic disorders in which the alteration of 
      several susceptibility genes results in dysfunctional mood regulation. However, 
      the molecular mechanisms underlying their transcriptional dysregulation are still 
      unclear. The transcription factor cyclic adenosine monophosphate (cAMP) response 
      element binding protein (CREB) and the neurotrophin brain-derived neurotrophic 
      factor (BDNF) have been implicated in rodent models of depression. We previously 
      provided evidence that Bdnf expression critically rely on a potent CREB 
      coactivator called CREB-regulated transcription coactivator 1 (CRTC1). METHODS: 
      To further evaluate the role of CRTC1 in the brain, we generated a knockout mouse 
      line and analyzed its behavioral and molecular phenotype. RESULTS: We found that 
      mice lacking CRTC1 associate neurobehavioral endophenotypes related to mood 
      disorders. Crtc1(-/-) mice exhibit impulsive aggressiveness, social withdrawal, 
      and decreased sexual motivation, together with increased behavioral despair, 
      anhedonia, and anxiety-related behavior in the novelty-induced hypophagia test. 
      They also present psychomotor retardation as well as increased emotional response 
      to stressful events. Crtc1(-/-) mice have a blunted response to the 
      antidepressant fluoxetine in behavioral despair paradigms, whereas fluoxetine 
      normalizes their aggressiveness and their behavioral response in the 
      novelty-induced hypophagia test. Crtc1(-/-) mice strikingly show, in addition to 
      a reduced dopamine and serotonin turnover in the prefrontal cortex, a concomitant 
      decreased expression of several susceptibility genes involved in neuroplasticity, 
      including Bdnf, its receptor TrkB, the nuclear receptors Nr4a1-3, and several 
      other CREB-regulated genes. CONCLUSIONS: Collectively, these findings support a 
      role for the CRTC1-CREB pathway in mood disorders etiology and behavioral 
      response to antidepressants and identify CRTC1 as an essential coactivator of 
      genes involved in mood regulation.
CI  - Copyright (c) 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All 
      rights reserved.
FAU - Breuillaud, Lionel
AU  - Breuillaud L
AD  - Center for Psychiatric Neuroscience, Prilly-Lausanne, Switzerland.
FAU - Rossetti, Clara
AU  - Rossetti C
FAU - Meylan, Elsa M
AU  - Meylan EM
FAU - Merinat, Christophe
AU  - Merinat C
FAU - Halfon, Olivier
AU  - Halfon O
FAU - Magistretti, Pierre J
AU  - Magistretti PJ
FAU - Cardinaux, Jean-Rene
AU  - Cardinaux JR
LA  - eng
GR  - 135692/SNSF_/Swiss National Science Foundation/Switzerland
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120515
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antidepressive Agents, Second-Generation)
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Crtc1 protein, mouse)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Transcription Factors)
RN  - 01K63SUP8D (Fluoxetine)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 5.4.- (Intramolecular Transferases)
RN  - EC 5.4.- (marneral synthase, Arabidopsis)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Aggression/drug effects/*physiology
MH  - Animals
MH  - Antidepressive Agents, Second-Generation/pharmacology/therapeutic use
MH  - Arabidopsis Proteins/metabolism
MH  - Biogenic Monoamines/metabolism
MH  - Brain/metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Corticosterone/blood
MH  - Depressive Disorder/drug therapy/*genetics/metabolism
MH  - Disease Models, Animal
MH  - Electroshock/adverse effects
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Exploratory Behavior/drug effects/physiology
MH  - Fear/drug effects/psychology
MH  - Female
MH  - Fluoxetine/pharmacology/therapeutic use
MH  - Food Preferences/drug effects/physiology
MH  - Gene Expression Regulation/*genetics
MH  - Hindlimb Suspension
MH  - Intramolecular Transferases/metabolism
MH  - Male
MH  - Maternal Behavior/drug effects/physiology
MH  - Maze Learning/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Nesting Behavior/drug effects/physiology
MH  - Neuronal Plasticity/drug effects/*genetics
MH  - Orphan Nuclear Receptors/genetics/metabolism
MH  - Receptor, trkB/genetics/metabolism
MH  - Sexual Behavior, Animal/drug effects/physiology
MH  - Signal Transduction/drug effects/*genetics
MH  - Social Behavior
MH  - Swimming/psychology
MH  - Transcription Factors/*deficiency/metabolism
EDAT- 2012/05/18 06:00
MHDA- 2013/02/07 06:00
CRDT- 2012/05/18 06:00
PHST- 2011/07/14 00:00 [received]
PHST- 2012/03/15 00:00 [revised]
PHST- 2012/04/07 00:00 [accepted]
PHST- 2012/05/18 06:00 [entrez]
PHST- 2012/05/18 06:00 [pubmed]
PHST- 2013/02/07 06:00 [medline]
AID - S0006-3223(12)00362-9 [pii]
AID - 10.1016/j.biopsych.2012.04.011 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2012 Oct 1;72(7):528-36. doi: 10.1016/j.biopsych.2012.04.011. 
      Epub 2012 May 15.