A metabolômica na compreensão de doenças neurológicas: análise untargeted de amostras de soro de bebês com microcefalia.

Abstract

Zika is a disease caused by the Zika virus (ZIKV), whose main form of transmission is through the bite of Aedes aegypti and Aedes albopictus mosquitoes. The disease has been registered in more than 80 countries worldwide. ZIKV infection has been associated with several neurological disorders and auditory and vision abnormalities. A concern in the medical community revolves around infection during the gestation period, as ZIKV affects fetal development and can lead to pregnancy complications. One of the main consequences is congenital microcephaly, a neurological anomaly that causes a reduction in the newborn's head circumference. The knowledge of the impact of ZIKV on metabolism is scarce and is essential for the development of treatments and understanding of pathogenesis. Metabolomics, a comprehensive and quantitative analysis of the metabolites present in a biological system, is an interesting tool to obtain information about the metabolic alterations of several diseases, including ZIKV infection. In this work, the metabolic profile of serum samples from newborns with positive diagnoses for ZIKV, with and without microcephaly was evaluated using untargeted metabolomics. Sample treatment involved protein precipitation, followed by derivatization, using oximation and silylation reactions for subsequent analysis by gas chromatography hyphenated to mass spectrometry (GC-MS). Data were processed in XCMS software and metabolites identified in AMDIS. Statistical analysis using univariate and multivariate methods was applied to find discriminating metabolites. The results showed significant changes in metabolic pathways of amino acids, organic acids, carbohydrates and derivatives. The biological interpretation of these alterations indicates that microcephaly is associated with a reduction in carbohydrate levels caused by virus replication. The increase of amino acid in patients with microcephaly reinforces this relationship due to the involvement of glycolysis intermediaries in amino acid synthesis. Little is known about the metabolic changes caused by infection with ZIKV, especially in newborns. Thus, the results obtained in this study provide relevant information on the association between Zika and cases of microcephaly.