A molecular cell biology of lithium

R. Williams, W. J. Ryves, E. C. Dalton, B. Eickholt, G. Shaltiel, G. Agam, A. J. Harwood

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Lithium (Li+), a mood stabilizer, has profound effects on cultured neurons, offering an opportunity to investigate its cellular biological effects. Here we consider the effect of Li+ and other psychotropic drugs on growth cone morphology and chemotaxis. Li+ inhibits GSK-3 (glycogen synthase kinase-3) at a therapeutically relevant concentration. Treated cells show a number of features that arise due to GSK-3 inhibition, such as altered microtubule dynamics, axonal branching and loss of semaphorin 3A-mediated growth cone collapse. Li+ also causes growth cones to spread; however, a similar effect is seen with two other mood stabilizers, valproic acid and carbamazepine, but without changes in microtubules or axon branching. This common effect of mood stabilizers is mediated by changes in inositol phosphate signalling, not GSK-3 activity. Given the presence of neurogenesis in the adult brain, we speculate that changes in growth cone behaviour could also occur during treatment of mental disorders.

Original languageEnglish
Pages (from-to)799-802
Number of pages4
JournalBiochemical Society Transactions
Volume32
Issue number5
DOIs
StatePublished - 1 Nov 2004

Keywords

  • Glycogen synthase kinase-3 (GSK-3)
  • Inositol
  • Lithium
  • Neuronal growth cone
  • Prolyl oligopeptidase
  • Valproic acid

ASJC Scopus subject areas

  • Biochemistry

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