title: Cytoskeleton involvement in lithium-induced SH-SY5Y neuritogenesis and the role of glycogen synthase kinase 3β.
abstract: Lithium modulates signals impacting on the cytoskeleton, a dynamic system contributing to neural plasticity at multiple levels. In this study, SH-SY5Y human neuronal cells were cultured in the absence (C) or in presence (Li) of a 0.5 mM Li2CO3 (i.e. 1 mM lithium ion) for 25-50 weeks. We investigated the effect of this treatment on (1) morphological changes of cells observed using Hemalun eosin staining assay, (2) cytoskeletal changes by indirect immunofluorescence (IIF) staining of microtubules (α-tubulin) and heavy neurofilaments subunits (NF-H) and by measuring the expression rate changes of genes coding for receptor for activated C kinase (RACK1), casein kinase2 (CK2) and thymosine beta-10 using cDNA arrays technology, (3) cell adhesion properties by IIF staining of β-catenin protein. Besides, we have tried to understand the molecular mechanism of lithium action that triggers changes in cytoskeleton and neurites outgrowth. Thus, we examined the effect of this treatment on glycogen synthase kinase 3 (GSK3) expression and activity using western blotting of GSK3 and phosphorylated β-catenin, a downstream GSK3 target protein. Our results showed that lithium treatment reduces axon length, increases axonal spreading, enhances neurites growth and neurites branching with an increase of growth cone size. Moreover, genes coding for CK2 and thymosine beta-10 were significantly up-regulated, however, that coding for RACK1 was down-regulated. The most interesting result in this work is that mechanism underlying lithium action was not related to the inhibition of GSK3 activity. In fact, neither expression rate nor activity of this protein was changed.
authors.affiliation: Laboratoire de Biologie Cellulaire, Faculté de Médecine Purpan, Universite Paul Sabatier Toulouse III, 37 Allées Jules Guesde, Toulouse, France, riadhsv@yahoo.fr.
authors.forename: Riadh
authors.initials: R
authors.lastname: Nciri
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Boujbiha
authors.forename: Samira
authors.initials: S
authors.lastname: Jbahi
authors.forename: Mohamed Salah
authors.initials: MS
authors.lastname: Allagui
authors.forename: Abdelfattah
authors.initials: A
authors.lastname: Elfeki
authors.forename: Christian
authors.initials: C
authors.lastname: Vincent
authors.forename: Françoise
authors.initials: F
authors.lastname: Croute
mesh_terms: D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D018020:Lithium Compounds / Q000378:metabolism / Q000494:pharmacology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D018020:Lithium Compounds; D018696:Neuroprotective Agents; D006006:Glycogen Synthase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3