Altered oxygen metabolism associated to neurogenesis of induced pluripotent stem cells derived from a schizophrenic patient

Authors: Bruna da Silveira Paulsen, Renata de Moraes Maciel, Antonio Galina, Mariana Souza da Silveira, Cleide dos Santos Souza, Hannah Drummond, Ernesto Nascimento Pozzatto, Hamilton Silva Junior, Leonardo Chicaybam, Raffael Massuda, Pedro Setti-Perdigao, Martin Bonamino, Paulo Silva Belmonte-de-Abreu, Newton Goncalves Castro, Helena Brentani, Stevens Kastrup Rehen

Source: Cell Transplantation

Publisher: Cognizant Communication Corporation

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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 post-mortem brains analyses or from non-neural cells. Here we describe that neural cells, derived from induced pluripotent stem cells generated from skin fibroblasts of a schizophrenic patient, presented a 2-fold increase in extra-mitochondrial 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.

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DOI: http://dx.doi.org/10.3727/096368911X600957

Appeared or available online: September 22, 2011