title: Altered oxygen metabolism associated to neurogenesis of induced pluripotent stem cells derived from a schizophrenic patient.
abstract: Schizophrenia has been defined as a neurodevelopmental disease that causes changes in the process of thoughts, perceptions, and emotions, usually leading to a mental deterioration and affective blunting. Studies have shown altered cell respiration and oxidative stress response in schizophrenia; however, most of the knowledge has been acquired from postmortem brain analyses or from nonneural cells. Here we describe that neural cells, derived from induced pluripotent stem cells generated from skin fibroblasts of a schizophrenic patient, presented a twofold increase in extramitochondrial oxygen consumption as well as elevated levels of reactive oxygen species (ROS), when compared to controls. This difference in ROS levels was reverted by the mood stabilizer valproic acid. Our model shows evidence that metabolic changes occurring during neurogenesis are associated with schizophrenia, contributing to a better understanding of the development of the disease and highlighting potential targets for treatment and drug screening.
authors.affiliation: Laboratório Nacional de Células-Tronco Embrionárias, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Bruna da Silveira
authors.initials: Bda S
authors.lastname: Paulsen
authors.forename: Renata
authors.initials: R
authors.lastname: de Moraes Maciel
authors.forename: Antonio
authors.initials: A
authors.lastname: Galina
authors.forename: Mariana
authors.initials: M
authors.lastname: Souza da Silveira
authors.forename: Cleide
authors.initials: C
authors.lastname: dos Santos Souza
authors.forename: Hannah
authors.initials: H
authors.lastname: Drummond
authors.forename: Ernesto
authors.initials: E
authors.lastname: Nascimento Pozzatto
authors.forename: Hamilton
authors.initials: H
authors.lastname: Silva
authors.forename: Leonardo
authors.initials: L
authors.lastname: Chicaybam
authors.forename: Raffael
authors.initials: R
authors.lastname: Massuda
authors.forename: Pedro
authors.initials: P
authors.lastname: Setti-Perdigão
authors.forename: Martin
authors.initials: M
authors.lastname: Bonamino
authors.forename: Paulo Silva
authors.initials: PS
authors.lastname: Belmonte-de-Abreu
authors.forename: Newton Gonçalves
authors.initials: NG
authors.lastname: Castro
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.forename: Stevens Kastrup
authors.initials: SK
authors.lastname: Rehen
mesh_terms: D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D008875:Middle Aged; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D055495:Neurogenesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000166:cytology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D014635:Valproic Acid