Disrupted intracellular calcium homeostasis through TRPM2/GSK3B in bipolar disorder

2013 Fiscal Year Final Research Report

• Project/Area Number: 24890078
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Psychiatric science
• Research Institution: University of Yamanashi
• Principal Investigator: UEMURA Takuji 山梨大学, 医学部附属病院, 助教 (60377497)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Keywords: 双極性障害 / 細胞内カルシウム制御 / TRPM2 / GSK3B / リチウム

Research Abstract

Disturbances of intracellular calcium homeostasis play important roles in the pathophysiology of bipolar disorder (BD). TRPM2 that is one of candidate genes for BD is a calcium-permeable cation channel activated by oxidative stress and induces cell death. Lithium is the most widely used for BD and induces the inhibition of GSK3B. Recently, Xie et al. reported that TRPM2 is associated with maintenance of the level of GSK-3B in mice hippocampal neurons. In this study, we sought to identify TRPM2/GSK3B cross-talk and confirm that the function of the BD-specific TRPM2 variant that has been found in our group. The expression level of TRPM2 was downed in the stable GSK3B knockdown U-87MG cell line. That of GSK3B was reduced in the stable TRPM2 knockdown U-87MG cells and the cell lines that were stable overexpression of BD-specific TRPM2 variant. We found TRPM2/GSK3B cross-talk and that BD-specific TRPM2 variant is reduced the expression of GSK3B.