Valproate reverts zinc and potassium imbalance in schizophrenia-derived reprogrammed cells

Schizophr Res. 2014 Apr;154(1-3):30-5. doi: 10.1016/j.schres.2014.02.007. Epub 2014 Mar 1.

Abstract

Schizophrenia has been considered a devastating clinical syndrome rather than a single disease. Nevertheless, the mechanisms behind the onset of schizophrenia have been only partially elucidated. Several studies propose that levels of trace elements are abnormal in schizophrenia; however, conflicting data generated from different biological sources prevent conclusions being drawn. In this work, we used synchrotron radiation X-ray microfluorescence spectroscopy to compare trace element levels in neural progenitor cells (NPCs) derived from two clones of induced pluripotent stem cell lines of a clozapine-resistant schizophrenic patient and two controls. Our data reveal the presence of elevated levels of potassium and zinc in schizophrenic NPCs. Neural cells treated with valproate, an adjunctive medication for schizophrenia, brought potassium and zinc content back to control levels. These results expand the understanding of atomic element imbalance related to schizophrenia and may provide novel insights for the screening of drugs to treat mental disorders.

Keywords: Induced pluripotent stem cells; Neural cells; Potassium; Schizophrenia; X-ray microfluorescence; Zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use
  • Cell Line
  • Clozapine / therapeutic use
  • Drug Resistance
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / metabolism
  • Potassium / metabolism*
  • Schizophrenia / drug therapy*
  • Schizophrenia / metabolism
  • Valproic Acid / pharmacology*
  • Zinc / metabolism*

Substances

  • Antipsychotic Agents
  • Valproic Acid
  • Zinc
  • Clozapine
  • Potassium