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.
Key Words
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Article info
Publication history
Published online: June 18, 2007
Accepted:
January 10,
2007
Received in revised form:
January 9,
2007
Received:
September 29,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
