202211201904
Status:
Tags: Genetics Psychiatry

Glycogen synthase kinase 3 beta

• Activated by Barr2/PP2A signaling complex downstream of dopamine D2 receptor activation
• Required for AKT/Barr2/PP2A complex formation
• Component of Wnt pathway where it regulates fate of beta-catenin, a transcription factor involved in neurodevelopment & other cellular functions
• Implicated in symptoms of neuropsychiatric disorders incl. SCZ, bipolar disorder, depression

Dysfunction

• Overexpression renders mice hyperactive whereas haploinsufficiency of GSK3B attenuates amph-induced locomotion
• Inhibitino of GSK3B inhibits D1R agonist SKF81297-mediated hyperlocomotion

Hyperdopaminergia

• In hyperdopaminergic levels, GSK3B is activated ins triatum in a D2Rand Barr2-dependent manner
• Pharmacological inhibition of GSK3B attenuates DA-dependent hyperlocomotion (similar to antipsychotics)

Pharmacology

• GSK3B is inhibited by antipsychotics, antidepressants, mood stabilizers
• Target of lithium & mediates action of lithium-sensitive behaviors incl. locomotion, forced-swim test, tail-suspension test (TST), and dark-light emergence test
• Not known if GSK3B signaling mediated by D2Rs is required for antipsychotic efficacy