title: Valproate reverts zinc and potassium imbalance in schizophrenia-derived reprogrammed cells.
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.
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Avenida Carlos Chagas, 373, bloco K, 2 andar, sala 27, Rio de Janeiro 21941, Brazil; D'Or Institute for Research Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro 22281, Brazil. Electronic address: bruna.paulsen@lance-ufrj.org.
authors.forename: Bruna da Silveira
authors.initials: Bda S
authors.lastname: Paulsen
authors.affiliation: Institute of Physics, Federal University of Rio de Janeiro, Av. Athos da Silveira Ramos, 149 Centro de Tecnologia, bloco A, Rio de Janeiro 21941, Brazil. Electronic address: simone@if.ufrj.br.
authors.forename: Simone Coutinho
authors.initials: SC
authors.lastname: Cardoso
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Avenida Carlos Chagas, 373, bloco K, 2 andar, sala 27, Rio de Janeiro 21941, Brazil. Electronic address: marianastelling@gmail.com.
authors.forename: Mariana Paranhos
authors.initials: MP
authors.lastname: Stelling
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Avenida Carlos Chagas, 373, bloco K, 2 andar, sala 27, Rio de Janeiro 21941, Brazil; D'Or Institute for Research Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro 22281, Brazil. Electronic address: danielcadilhe@lance-ufrj.org.
authors.forename: Daniel Veloso
authors.initials: DV
authors.lastname: Cadilhe
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Avenida Carlos Chagas, 373, bloco K, 2 andar, sala 27, Rio de Janeiro 21941, Brazil; D'Or Institute for Research Education (IDOR), Rua Diniz Cordeiro, 30, Rio de Janeiro 22281, Brazil. Electronic address: srehen@lance-ufrj.org.
authors.forename: Stevens Kastrup
authors.initials: SK
authors.lastname: Rehen
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D003024:Clozapine / Q000627:therapeutic use; D004351:Drug Resistance; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy* / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*; D015032:Zinc / Q000378:metabolism*
chemical_list: D014150:Antipsychotic Agents; D014635:Valproic Acid; D015032:Zinc; D003024:Clozapine; D011188:Potassium
keywords: Induced pluripotent stem cells; Neural cells; Potassium; Schizophrenia; X-ray microfluorescence; Zinc