Cytoskeleton involvement in lithium-induced SH-SY5Y neuritogenesis and the role of glycogen synthase kinase 3β

• Published in: Aging clinical and experimental research Vol. 27; no. 3; pp. 255 - 263
• Main Authors: Nciri, Riadh, Boujbiha, Mohamed Ali, Jbahi, Samira, Allagui, Mohamed Salah, Elfeki, Abdelfattah, Vincent, Christian, Croute, Françoise
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.06.2015; Springer Nature B.V
• Subjects: Cell adhesion & migration; Cells, Cultured; Cytoskeleton; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Geriatrics/Gerontology; Glycogen Synthase - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Humans; Kinases; Lithium; Lithium Compounds - metabolism; Lithium Compounds - pharmacology; Medicine; Medicine & Public Health; Nerve Degeneration - drug therapy; Nerve Degeneration - metabolism; Neurites - metabolism; Neurogenesis - drug effects; Neuronal Plasticity - drug effects; Neuroprotective Agents - metabolism; Neuroprotective Agents - pharmacology; Original Article; Proteins; Treatment Outcome; Lithium; Cytoskeleton; Neuritogenesis; GSK3
• ISSN: 1720-8319; 1594-0667; 1720-8319
• DOI: 10.1007/s40520-014-0290-3

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 Li 2 CO 3 (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.