کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4180373 1276600 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Lithium Reduces FoxO3a Transcriptional Activity by Decreasing Its Intracellular Content
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Lithium Reduces FoxO3a Transcriptional Activity by Decreasing Its Intracellular Content
چکیده انگلیسی

BackgroundForkhead 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.MethodsTranscriptional activity, target gene expression, and protein levels of FoxO3a were measured in cultured cells and mouse brain after lithium treatment.ResultsLithium 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.ConclusionsLithium, 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 62, Issue 12, 15 December 2007, Pages 1423–1430
نویسندگان
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