GSK-3 and Wnt signaling in neurogenesis and bipolar disorder

Abstract

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The 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 Wnt pathway and therefore also plays a central role in neural development and adult neurogenesis. As lithium, the first line of therapy for bipolar disorder (BPD), activates Wnt signaling by inhibiting GSK-3, much attention has focused on GSK-3 and Wnt signaling in the therapeutic response to lithium. However, GSK-3 also regulates other critical signaling pathways, 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 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.

Keywords

• Behavior
• Bipolar Disorder
• Lithium
• Neurogenesis
• development
• Wnt