Biochem. Soc. Trans (2004) 32, 799-802 - R. Williams and others

Medline/PubMed Citation | Related Articles in PubMed | Download to Citation Manager

Biochemical Society Transactions (2004) 32, (799–802) (Printed in Great Britain)

PDF

Legacy HTML

Send to a friend

Add a comment

Focus Topics at BioScience2004

A molecular cell biology of lithium

R. Williams*, W.J. Ryves*, E.C. Dalton*, B. Eickholt†, G. Shaltiel‡, G. Agam‡ and A.J. Harwood*¹

*MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower St, London WC1E 6BT, U.K., †MRC Centre for Developmental Neurobiology, King's College London, Guy's Hospital Campus, London SE1 1UL, U.K., and ‡Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Key words: glycogen synthase kinase-3 (GSK-3), inositol, lithium, neuronal growth cone, prolyl oligopeptidase, valproic acid.

Abbreviations used: Ab, b-amyloid protein; CBZ, carbamazepine; DRG, dorsal root ganglion(-lia); F-actin, filamentous actin; GSK-3, glycogen synthase kinase-3; PI3K, phosphoinositide 3-kinase; PIP, phosphatidylinositol phosphate; PIP₂, phosphatidylinositol 4,5-bisphosphate; PKB, protein kinase B; PO, prolyl oligopeptidase; Sema3A, semaphorin 3A; VPA, valproic acid.

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.