Altered Oxygen Metabolism Associated to Neurogenesis of Induced Pluripotent Stem Cells Derived From a Schizophrenic Patient

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.

Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

Instituto Nacional de Ciencia e Tecnologia (INCTC)

Instituto Nacional de Ciencia e Tecnologia (INCTC)

Instituto do Milenio-Terapia Genica (CNPq)

Instituto do MilenioTerapia Genica (CNPq)

Instituto Nacional do Cancer (INCA)

Instituto Nacional do Cancer (INCA)

INCT for Excitotoxicity and Neuroprotection/CNPq

INCT for Excitotoxicity and Neuroprotection/CNPq