25.3 OLIGODENDROCYTES MEDIATE ENERGY METABOLISM ALTERATIONS IN SCHIZOPHRENIA: A PROTEOMIC STUDY

摘要

BackgroundWhile comparing the proteomes and subproteomes of 8 post-mortem brain regions and cerebrospinal fluid from schizophrenia patients to controls, we consistently observed alterations in energy metabolism, cell growth and maintenance, synaptic function, and myelinization processes. Considering the nature of these analyses, it was not possible to reveal which particular cell types display such alterations. This is essential information given increasing evidence of glia cells as pivotal players in schizophrenia. With this in mind, we analyzed the proteomes and phosphoproteomes of cultured astrocytes, oligodendrocytes and neurons treated with MK-801, a NMDA-receptor antagonist which impairs glutamatergic transmission as postulated in schizophrenia. We also analyzed biochemical pathways modulated by typical and atypical antipsychotics in human oligodendrocytes. Results led us to employ induced pluripotent stem cell-derived cerebral organoids to deepen our understanding of the data. The central aim of this study is to depict which cell type(s) present proteome changes similarly to those we found in our earlier analysis of human brain tissue as well as identify key pathways for an effective antipsychotic response.