Hypoxia activates glycogen synthase kinase-3 in mouse brain in vivo: Protection by mood stabilizers and imipramine

Myoung Sun Roh, Tae Yeon Eom, Anna A. Zmijewska, Patrizia De Sarno, Kevin A. Roth, Richard S. Jope

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Glycogen synthase kinase-3 (GSK3), which is primarily regulated by an inhibitory phosphorylation of an N-terminal serine, has been implicated as contributing to mood disorders by the finding that it is inhibited by the mood stabilizer lithium. This study tested if the antidepressant imipramine or the mood stabilizers lithium and sodium valproate regulated pathophysiological serine-dephosphorylation of GSK3 caused by hypoxia in mouse brain in vivo. Hypoxia caused rapid serine-dephosphorylation of both isoforms of GSK3, GSK3β and GSK3α, in mouse cerebral cortex, hippocampus, and striatum. Pretreatment of mice with imipramine, sodium valproate, or lithium attenuated hypoxia-induced serine-dephosphorylation of GSK3β and GSK3α in all three brain regions. These results demonstrate that imipramine and mood stabilizers are capable of blocking pathophysiologically induced serine-dephosphorylation of GSK3, supporting the hypothesis that stabilization of serine-phosphorylation of GSK3 contributes to their therapeutic effects.

Original languageEnglish (US)
Pages (from-to)278-286
Number of pages9
JournalBiological Psychiatry
Volume57
Issue number3
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Keywords

  • Glycogen synthase kinase-3
  • hypoxia
  • imipramine
  • lithium
  • mood disorders
  • valproate

ASJC Scopus subject areas

  • Biological Psychiatry

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