PMID- 21740920
OWN - NLM
STAT- MEDLINE
DCOM- 20120813
LR  - 20221207
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 62
IP  - 1
DP  - 2012 Jan
TI  - Stress-induced activation of the brainstem Bcl-xL gene expression in rats treated 
      with fluoxetine: correlations with serotonin metabolism and depressive-like 
      behavior.
PG  - 177-83
LID - 10.1016/j.neuropharm.2011.06.016 [doi]
AB  - Mechanisms underlying stress-induced depression and antidepressant drug action 
      were shown to involve alterations in serotonergic (5-HT) neurotransmission and 
      expression of genes coding for proteins associated with neurotrophic signaling 
      pathways and cell-survival in the hippocampus and cortex. Expression of these 
      genes in the brainstem containing 5-HT neurons may also be related to 
      vulnerability or resilience to stress-related psychopathology. Here we 
      investigated 5-HT markers and expression of genes for Brain-Derived Neurotrophic 
      Factor (BDNF) and apoptotic proteins in the brainstem in relation to swim 
      stress-induced behavioral despair. We found that anti-apoptotic Bcl-xL gene is 
      sensitive to stress during the course of fluoxetine administration. 
      Responsiveness of this gene to stress appeared concomitantly with an 
      antidepressant-like effect of fluoxetine in the forced swim test. Bcl-xL 
      transcript levels showed negative correlations with duration of immobility in the 
      test and 5-HT turnover in the brainstem. In contrast, BDNF and pro-apoptotic 
      protein Bax mRNA levels were unchanged by either fluoxetine or stress, suggesting 
      specificity of Bcl-xL gene responses to these treatments. We also found that the 
      levels of mRNAs for tryptophan hydroxylase-2 (TPH2) and 5-HT transporter (5-HTT) 
      were significantly down-regulated following prolonged treatment with fluoxetine, 
      but were not affected by stress. Unlike TPH2 and 5-HTT, 5-HT1A receptor mRNA 
      levels were not altered by fluoxetine but significantly increased in response to 
      swim stress. These data show that long-term fluoxetine treatment leads to changes 
      in 5-HT and Bcl-xL responses to stress associated with antidepressant-like 
      effects of the drug. This article is part of a Special Issue entitled 'Anxiety 
      and Depression'.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Shishkina, Galina T
AU  - Shishkina GT
AD  - Functional Neurogenomics Laboratory, Institute of Cytology and Genetics, 
      Novosibirsk 630090, Russia.
FAU - Kalinina, Tatyana S
AU  - Kalinina TS
FAU - Berezova, Inna V
AU  - Berezova IV
FAU - Dygalo, Nikolay N
AU  - Dygalo NN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110629
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Bcl2l1 protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (bcl-X Protein)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - EC 1.14.16.4 (Tryptophan Hydroxylase)
RN  - EC 1.14.16.4 (tph2 protein, rat)
SB  - IM
MH  - Animals
MH  - Brain Stem/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Disease Models, Animal
MH  - Fluoxetine/*therapeutic use
MH  - Gene Expression Regulation/drug effects
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Serotonin, 5-HT1A/genetics/metabolism
MH  - Serotonin/genetics/*metabolism
MH  - Serotonin Plasma Membrane Transport Proteins/genetics/metabolism
MH  - Selective Serotonin Reuptake Inhibitors/*therapeutic use
MH  - Statistics as Topic
MH  - *Stress, Psychological/drug therapy/metabolism/pathology
MH  - Swimming/psychology
MH  - Tryptophan Hydroxylase/genetics/metabolism
MH  - bcl-2-Associated X Protein/genetics/metabolism
MH  - bcl-X Protein/*metabolism
EDAT- 2011/07/12 06:00
MHDA- 2012/08/14 06:00
CRDT- 2011/07/12 06:00
PHST- 2011/04/29 00:00 [received]
PHST- 2011/06/16 00:00 [revised]
PHST- 2011/06/17 00:00 [accepted]
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2012/08/14 06:00 [medline]
AID - S0028-3908(11)00260-7 [pii]
AID - 10.1016/j.neuropharm.2011.06.016 [doi]
PST - ppublish
SO  - Neuropharmacology. 2012 Jan;62(1):177-83. doi: 10.1016/j.neuropharm.2011.06.016. 
      Epub 2011 Jun 29.