GSK-3 and Wnt Signaling in Neurogenesis and Bipolar Disorder

• Published in: Frontiers in molecular neuroscience Vol. 5; p. 1
• Main Authors: Valvezan, Alexander J, Klein, Peter S
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 01.01.2012; Frontiers Media S.A
• Subjects: AKT protein; Behavior; Bipolar Disorder; Central nervous system; development; Embryos; Glycogen; Glycogen synthase kinase 3; Lithium; Neurogenesis; Neuroscience; Signal transduction; Wnt; Wnt protein; psychiatric; lithium; bipolar disorder; development; neurogenesis; GSK-3; Wnt; behavior
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2012.00001

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.