title: Neuroprotective effects of chronic exposure of SH-SY5Y to low lithium concentration involve glycolysis stimulation, extracellular pyruvate accumulation and resistance to oxidative stress.
abstract: Recent studies suggest that lithium protects neurons from death induced by a wide array of neurotoxic insults, stimulates neurogenesis and could be used to prevent age-related neurodegenerative diseases. In this study, SH-SY5Y human neuronal cells were cultured in the absence (Con) or in the presence (Li+) of a low lithium concentration (0.5 mm Li2CO3, i.e. 1 mm lithium ion) for 25-50 wk. In the course of treatment, growth rate of Con and Li+ cells was regularly analysed using Alamar Blue dye. Resistance to oxidative stress was investigated by evaluating: (1) the adverse effects of high concentrations of lithium (4-8 mm) or glutamate (20-90 mm) on cell growth rate; (2) the levels of lipid peroxidation (TBARS) and total glutathione; (3) the expression levels of the anti-apoptotic Bcl-2 protein. In addition, glucose metabolism was investigated by analysing selected metabolites in culture media and cell extracts by 1H-NMR spectroscopy. As compared to Con, Li+ cells multiplied faster and were more resistant to stress, as evidenced by a lower dose-dependent decrease of Alamar Blue reduction and dose-dependent increase of TBARS levels induced by toxic doses of lithium and glutamate. Total glutathione content and Bcl-2 level were increased in Li+ cells. Glucose consumption and glycolytic activity were enhanced in Li+ cells and an important release of pyruvate was observed. We conclude that chronic exposure to lithium induces adaptive changes in metabolism of SH-SY5Y cells involving a higher cell growth rate and a better resistance to oxidative stress.
authors.affiliation: Laboratoire de Biologie Cellulaire, Faculté de Médecine Purpan, Université Paul Sabatier Toulouse III, 37 Allées Jules Guesde, Toulouse, France. riadhsv@yahoo.fr
authors.forename: Riadh
authors.initials: R
authors.lastname: Nciri
authors.forename: Frank
authors.initials: F
authors.lastname: Desmoulin
authors.forename: Mohamed Saleh
authors.initials: MS
authors.lastname: Allagui
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Murat
authors.forename: Abdelfattah El
authors.initials: AE
authors.lastname: Feki
authors.forename: Christian
authors.initials: C
authors.lastname: Vincent
authors.forename: Françoise
authors.initials: F
authors.lastname: Croute
mesh_terms: D000704:Analysis of Variance; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D016651:Lithium Carbonate / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017392:Thiobarbituric Acid Reactive Substances; D016651:Lithium Carbonate; D019289:Pyruvic Acid; D005978:Glutathione