title: Neuronal distress induced by low extracellular sodium in vitro is partially reverted by the return to normal sodium.
abstract: BACKGROUND
  Hyponatremia is associated with negative clinical outcomes even when chronic and mild. It is also known that hyponatremia treatment should be appropriately performed, to avoid dramatic consequences possibly leading to death. We have previously demonstrated that chronically low extracellular [Na(+)], independently of reduced osmolality, is associated with signs of neuronal cell distress, possibly involving oxidative stress.
  
  
  OBJECTIVE
  The aim of the present study was to assess whether the return to normal extracellular [Na(+)] is able to revert neuronal cell damage.
  
  
  METHODS
  After exposing SH-SY5Y and SK-N-AS cells to low [Na(+)] and returning to normal [Na(+)], we analyzed cell viability by MTS assay, ROS accumulation by FASCan and expression of anti-apoptotic genes.
  
  
  RESULTS
  We found that the viability of cells was restored upon return to normal [Na(+)]. However, when more subtle signs of cell distress were assessed, such as the expression level of the anti-apoptotic genes Bcl-2 and DHCR24 or of the heme oxygenase 1 gene, a complete return to basal values was not observed, in particular in SK-N-AS, even when [Na(+)] was gradually increased. We also demonstrated that the amount of ROS significantly increased in low [Na(+)], thus confirming that oxidative stress appears to contribute to the effects of low [Na(+)] on cell homeostasis.
  
  
  CONCLUSIONS
  Overall, this study provided the first demonstration that the correction of chronically low extracellular [Na(+)] may not be able to revert all the cell alterations associated with reduced [Na(+)]. These results suggest that prompt hyponatremia treatment might prevent possible residual abnormalities.
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 50139, Florence, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Benvenuti
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 50139, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Deledda
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 50139, Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Luciani
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 50139, Florence, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Giuliani
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 50139, Florence, Italy.
authors.forename: B
authors.initials: B
authors.lastname: Fibbi
authors.affiliation: Andrology Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50139, Florence, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Muratori
authors.affiliation: Endocrine Unit, "Center for Research, Transfer and High Education on Chronic, Inflammatory, Degenerative and Neoplastic Disorders for the Development of Novel Therapies" (DENOThe), Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 50139, Florence, Italy. alessandro.peri@unifi.it.
authors.forename: A
authors.initials: A
authors.lastname: Peri
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D045604:Extracellular Fluid / Q000378:metabolism; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007010:Hyponatremia / Q000378:metabolism / Q000628:therapy; D007700:Kinetics; D015227:Lipid Peroxidation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D064587:Osmoregulation; D009997:Osmotic Pressure; D018384:Oxidative Stress; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017154:Stromal Cells / Q000502:physiology*
chemical_list: C000595707:BCL2 protein, human; D015415:Biomarkers; D009419:Nerve Tissue Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human
keywords: Hyponatremia; Nervous system; Neuronal distress; Osmolality; Oxidative stress