PMID- 17574214
OWN - NLM
STAT- MEDLINE
DCOM- 20080227
LR  - 20161124
IS  - 1873-2402 (Electronic)
IS  - 0006-3223 (Linking)
VI  - 62
IP  - 12
DP  - 2007 Dec 15
TI  - Lithium reduces FoxO3a transcriptional activity by decreasing its intracellular 
      content.
PG  - 1423-30
AB  - BACKGROUND: Forkhead box, class O (FoxO) transcription factors play important 
      roles in cell fate, differentiation, survival, and stress regulation. A subtype 
      of mammalian FoxO transcription factors, FoxO3a, is widely distributed in the 
      brain, and its activity is regulated by neurotrophins, such as brain-derived 
      neurotrophic factor (BDNF), resulting in transcriptional inactivation of FoxO3a. 
      Searching for therapeutic targets downstream of BDNF signaling will facilitate 
      the development of new treatment approaches for mood disorders. METHODS: 
      Transcriptional activity, target gene expression, and protein levels of FoxO3a 
      were measured in cultured cells and mouse brain after lithium treatment. RESULTS: 
      Lithium significantly reduced FoxO3a transcriptional activity and gene 
      expression. The effect of lithium may be the result of a significant reduction of 
      the FoxO3a protein levels in both the cytosol and nucleus that was mediated by an 
      Akt-independent action. More importantly, this effect of lithium was observed in 
      cells and mouse brain after therapeutically relevant lithium treatments. 
      CONCLUSIONS: Lithium, an established treatment for mood disorders, has a 
      prominent effect on FoxO3a transcriptional activity and the effect is likely 
      therapeutically relevant. These results warrant further study to identify if 
      FoxO3a is a transcriptional target in the neuropathology and treatment of mood 
      disorders.
FAU - Mao, Zhengquan
AU  - Mao Z
AD  - Department of Psychiatry and Behavioral Neurobiology, University of Alabama at 
      Birmingham, Birmingham, Alabama 35294-0017, USA.
FAU - Liu, Liqin
AU  - Liu L
FAU - Zhang, Rusheng
AU  - Zhang R
FAU - Li, Xiaohua
AU  - Li X
LA  - eng
GR  - MH064555/MH/NIMH NIH HHS/United States
GR  - MH073723/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070615
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Antipsychotic Agents)
RN  - 0 (FOXO3 protein, human)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 9FN79X2M3F (Lithium)
SB  - IM
MH  - Animals
MH  - Antipsychotic Agents/*pharmacology
MH  - Brain/drug effects/metabolism
MH  - Cell Line
MH  - Chromatin Immunoprecipitation/methods
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors/genetics/*metabolism
MH  - Gene Expression/*drug effects
MH  - Humans
MH  - Intracellular Fluid/*drug effects
MH  - Lithium/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation/physiology
MH  - Neuroblastoma/pathology
MH  - Transfection/methods
EDAT- 2007/06/19 09:00
MHDA- 2008/02/28 09:00
CRDT- 2007/06/19 09:00
PHST- 2006/09/29 00:00 [received]
PHST- 2007/01/09 00:00 [revised]
PHST- 2007/01/10 00:00 [accepted]
PHST- 2007/06/19 09:00 [pubmed]
PHST- 2008/02/28 09:00 [medline]
PHST- 2007/06/19 09:00 [entrez]
AID - S0006-3223(07)00054-6 [pii]
AID - 10.1016/j.biopsych.2007.01.006 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2007 Dec 15;62(12):1423-30. doi: 10.1016/j.biopsych.2007.01.006. 
      Epub 2007 Jun 15.