PMID- 14735135
OWN - NLM
STAT- MEDLINE
DCOM- 20040517
LR  - 20150311
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 29
IP  - 4
DP  - 2004 Apr
TI  - Drug-induced decrease of protein kinase a activity reveals alteration in BDNF 
      expression of bipolar affective disorder.
PG  - 805-12
AB  - Bipolar affective disorder (BAD) is a severe disease whose molecular and cellular 
      bases are not well known. The aim of the present study was to probe the cAMP 
      signaling downstream targets by pharmacologically manipulating the protein kinase 
      A (PKA) enzyme, along with the assessment of brain-derived neurotrophic factor 
      (BDNF) expression in lymphoblasts. The time course of lymphoblast PKA activity 
      (up to 72 h) revealed optimal activity at 24 h. Then, the enzyme activity and 
      protein levels of PKA Calpha subunit and phopsho-cAMP responsive element binding 
      (CREB) were assayed in lymphoblasts derived from 12 BAD and 12 control (CT) 
      subjects and cultured for 24 h in the presence of cAMP analog drugs. The results 
      indicated that basal PKA activity and PKA Calpha subunit immunolabeling are 
      increased in cells from BAD compared with controls. Enzyme activity was increased 
      by Sp-isomer in BAD and in CT's cells, without change in protein levels. In 
      contrast, the Rp-isomer decreased enzyme activity and protein levels. In 
      drug-naive conditions, there was no change in BDNF expression of BAD cells 
      compared with CT cells. Treatment with Sp-isomer induced increased BDNF in both 
      groups, while treatment with Rp-isomer induced a significant decrease in BDNF 
      expression of BAD compared with CT. The p-CREB changes followed changes in BDNF 
      levels, with increased and decreased Sp-isomer and Rp-isomer treatment, 
      respectively. Our results suggest that mood disorder is associated with PKA 
      upregulation and this could mask alteration in BDNF expression, because slowing 
      down of PKA signaling results in a decrease of BDNF expression. These findings, 
      combined with previous reports, provide a new insight to explain pharmacological 
      features in different diagnostic groups.
FAU - Karege, Felicien
AU  - Karege F
AD  - Geneva University Hospitals (Belle-Idee), Division of Neuropsychiatry, 
      Chene-Bourg (Geneva), Switzerland. felicien.karege@biolo.unige.ch
FAU - Schwald, Michele
AU  - Schwald M
FAU - El Kouaissi, Rachid
AU  - El Kouaissi R
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Activating Transcription Factor 1)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - 8-Bromo Cyclic Adenosine Monophosphate/*pharmacology
MH  - Activating Transcription Factor 1
MH  - Adult
MH  - Bipolar Disorder/*enzymology/genetics/metabolism/pathology
MH  - Blotting, Western/methods
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/genetics/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/*metabolism
MH  - *DNA-Binding Proteins
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Lymphocyte Activation
MH  - Lymphocytes/drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - Protein Subunits/metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Time Factors
MH  - Transcription Factors/genetics/metabolism
EDAT- 2004/01/22 05:00
MHDA- 2004/05/18 05:00
CRDT- 2004/01/22 05:00
PHST- 2004/01/22 05:00 [pubmed]
PHST- 2004/05/18 05:00 [medline]
PHST- 2004/01/22 05:00 [entrez]
AID - 1300384 [pii]
AID - 10.1038/sj.npp.1300384 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2004 Apr;29(4):805-12. doi: 10.1038/sj.npp.1300384.