Understanding the influence of glycolysis components in the function of oligodendrocytes: linking with findings in schizophrenia

Abstract

Schizophrenia is a chronic, severe and disabling psychiatric disorder that may affect up to 1% of population worldwide. The prevailing hypothesis for schizophrenia´s etiology is that disturbances in different levels of multiple risk genes, each one contributing a subtle effect, interact with environmental stimuli impacting brain development and function. Several methodologies, such as those employed in imaging, transcriptomics and proteomics studies, have been used in order to understand the molecular basis of schizophrenia. These studies have associated to the development and the establishment of this mental disorder dysfunctions in energy metabolism oligodendrocyte function. The aim of present project is to link these two components. We will characterize biochemical and morphological profiles using proteomic and microscopy techniques of oligodendrocyte precursor cells and myelinating oligodendrocytes subjected to overexpression and knock-down of glycolytic enzymes that such as aldolase C that we found differentially expressed in schizophrenia brains. With this, we hope to identify proteins and biochemical pathways affected by aldolase C modulation as well as its influence on morphology and function (myelination) of oligodendrocytes. Obtained data will be compared to previous findings in patients in order to observe whether the overexpression or knock-down of aldolase C is able to generate disturbances similar to those observed in schizophrenia. This study will contribute to understanding of the biochemical mechanisms involved in schizophrenia pathogenesis as well as the identification of key molecules that can be further studied, pointing out new therapeutic targets. (AU)