Regulação da expressão de genes relacionados à matriz extracelular em fibroblastos dérmicos de pacientes com esquizofrenia

Abstract

Psychiatric disorders such schizophrenia and bipolar disorder share importante aspects like commom gene risk, neurophisiologic deficit, defense antioxidante system deregulation and prefrontal cortex glutathione deficit. Extracellular matrix (ECM) components anomalies from central nervous system (CNS) are observed in neurological disorders and have been discuted in psychiatric disorders. The ECM from SNC has important functions such synaptic maintenance, control of neuronal plasticity, protection of neurons againts oxidative stress, cellular sinalization and growth factores resevoir. However, after multiple injuries, stress or disease, the remodelation capacity exerced by ECM becomes compromized, leading to failures in the neuron comunication and ECM regenerative capacity. Oxidative stress have been suggested as causes for anomalies seen in schizophrenia ECM. The propose of this study was validate some genes related to extracellular matrix which were differentially expressed between schizophrenic patients and controls observed in our previous study using microarray. Furthemore, we asked how oxidative stress can regulate these genes in schizophrenia and if this regulation is it similiar with bipolar disorder. For this, we used skin fibroblastos culture from residual schizophrenic and bipolar euthimic patients. The culture were treated with tBHQ, a compound which induces oxidative stress, and after the treatment we extracted the mRNA for genetic expression of MMP16, GALNT6, SULF1, ADAMTS1 and ACSL1. We can not validade the expression diferences of five genes selected between schizophrenic patients and controles and bipolar patients compared to respectives controls. But, it was observed that the five genes selected are regulated by oxidative stress in schizophrenic and bipolar patients. Besides, the protein analysis revealed galnac transferase 6 levels are decreased in schizophrenic patients, suggesting a glycosylation reduced of ECM components, which can be compromise the matrix stability. ADAMTS1 gene levels have a tendency of increase in bipolar patients, also suggesting a impairment in integrity ECM componentes. In general, the data from gene expression of schizoprenic and bipolar patients are similar. Oxidative stress alter the regulation of gene extracelular matrix associated in schizophrenia and bipolar disorder. Functional studies related to enzymes codified by GALNT6 and ADAMTS1 are necessary to better understand the relation of both in schizophrenia and bipolar disorder pathophysiology