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.
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November 2004
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Conference Article|
October 26 2004
A molecular cell biology of lithium
R. Williams;
R. Williams
*MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower St, London WC1E 6BT, U.K.
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W.J. Ryves;
W.J. Ryves
*MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower St, London WC1E 6BT, U.K.
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E.C. Dalton;
E.C. Dalton
*MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower St, London WC1E 6BT, U.K.
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B. Eickholt;
B. Eickholt
†MRC Centre for Developmental Neurobiology, King's College London, Guy's Hospital Campus, London SE1 1UL, U.K.
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G. Shaltiel;
G. Shaltiel
‡Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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G. Agam;
G. Agam
‡Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
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A.J. Harwood
A.J. Harwood
1
*MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower St, London WC1E 6BT, U.K.
1To whom correspondence should be addressed (email a.harwood@ucl.ac.uk).
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Publisher: Portland Press Ltd
Received:
July 23 2004
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2004 The Biochemical Society
2004
Biochem Soc Trans (2004) 32 (5): 799–802.
Article history
Received:
July 23 2004
Citation
R. Williams, W.J. Ryves, E.C. Dalton, B. Eickholt, G. Shaltiel, G. Agam, A.J. Harwood; A molecular cell biology of lithium. Biochem Soc Trans 1 November 2004; 32 (5): 799–802. doi: https://doi.org/10.1042/BST0320799
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