Lithium-induced activation of Akt and CaM kinase II contributes to its neuroprotective action in a rat microsphere embolism model

Takuya Sasaki, Feng Han, Norifumi Shioda, Shigeki Moriguchi, Jiro Kasahara, Koichi Ishiguro, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

Lithium used in bipolar mood disorder therapy protects neurons from brain ischemic cell death. Here, we documented that lithium administration under microsphere-embolism (ME)-induced brain ischemia restored decreased protein kinase B (Akt) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activities 24 h after ischemia in rat brain. Akt activation was associated with increased phosphorylation of its potential targets forkhead transcription factor (FKHR) and glycogen synthase kinase-3β (GSK-3β). In parallel with decreased CaMKII autophosphorylation, we also found marked dephosphorylation of tau proteins 24-72 h after ME. Increased protein phosphatase 2A (PP2A) activity was found 24 h after ME. Inhibition of increased PP2A activity by lithium treatment apparently mediated restored tau phosphorylation. Taken together, activation of Akt and CaMKII by lithium was associated with neuroprotective activity in ME-induced neuronal injury.

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalBrain research
Volume1108
Issue number1
DOIs
Publication statusPublished - 2006 Sep 7

Keywords

  • Akt
  • CaM kinase II
  • Glycogen synthase kinase-3β
  • Lithium
  • Microsphere embolism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Lithium-induced activation of Akt and CaM kinase II contributes to its neuroprotective action in a rat microsphere embolism model'. Together they form a unique fingerprint.

Cite this