AUTHOR=Valvezan Alexander J., Klein Peter S. TITLE=GSK-3 and Wnt Signaling in Neurogenesis and Bipolar Disorder JOURNAL=Frontiers in Molecular Neuroscience VOLUME=Volume 5 - 2012 YEAR=2012 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2012.00001 DOI=10.3389/fnmol.2012.00001 ISSN=1662-5099 ABSTRACT=

The canonical Wnt signaling pathway is critical for development of the mammalian central nervous system and regulates diverse processes throughout adulthood, including adult neurogenesis. Glycogen synthase kinase-3 (GSK-3) antagonizes the canonical Wnt pathway and therefore also plays a central role in neural development and adult neurogenesis. Lithium, the first line of therapy for bipolar disorder, inhibits GSK-3, activates Wnt signaling and stimulates adult neurogenesis, which may be important for its therapeutic effects. GSK-3 also regulates other critical signaling pathways which may contribute to the therapeutic effects of lithium, including growth factor/neurotrophin signaling downstream of Akt. Here we will review the roles of GSK-3 in CNS development and adult neurogenesis, with a focus on the canonical Wnt pathway. We will also discuss the validation of GSK-3 as the relevant target of lithium and the mechanisms downstream of GSK-3 that influence mammalian behavior.