Seminários em Neurociências 2011.1

Segunda-feira 30/05/2011 10:50h Sala 4 – Escola de Ciência e Tecnologia

Effects of a nitric oxide donor in patients with schizophrenia

João Paulo Maia de Oliveira (Depto. Medicina Clínica/UFRN; IINN-ELS)

“Schizophrenia is arguably the worst disease affecting mankind, even AIDS not excepted”. Since this historic statement by the editors of Nature in 1988, schizophrenia remains a treatment challenge, with few novel developments in pharmacotherapy. Although the search for causes continues, the most recent genetic data indicate that mechanisms such as neuroimmunoinflammation may be more prominent than previously thought. There is also evidence indicating that such neuroimmunoinflammatory changes in schizophrenia may lead to abnormalities of the glutamate-nitric oxide (NO) network. Indeed, it is well established that NO is involved in development of abnormal behavior resembling psychosis. Strikingly, in preclinical experiments we have observed that sodium nitroprusside (SNP) completely abolished the effect of phencyclidine (a blocker of N-methyl-D-aspartate (NMDA) glutamate receptors that induces psychosis-like behavior) and enhanced molecular expression of c-fos, an immediate early gene which is an indirect marker of neuronal activity. The precise mechanism by which SNP produces such dramatic effects in phencyclidine-treated animals remains unclear. However, in addition to generating NO in the brain and increasing cyclic guanosine monophosphate (GMP) production, it may also have direct activity at the NMDA receptor. Preclinical observations led us to develop the research hypothesis that SNP may improve symptoms of schizophrenia. These preclinical observations led us to develop the research hypothesis that SNP may improve symptoms of schizophrenia.