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Free keywords:
glial cells, oligodendrocyte, proteomics, schizophrenia, pharmacology, clozapine, MK801
Abstract:
Separate lines of evidence have demonstrated the involvement of
N-methyl-D-aspartate (NMDA) receptor and oligodendrocyte dysfunctions in
schizophrenia. Here, we have carried out shotgun mass spectrometry
proteome analysis of oligodendrocytes treated with the NMDA receptor
antagonist MK-801 to gain potential insights into these effects at the
molecular level. The MK-801 treatment led to alterations in the levels
of 68 proteins, which are associated with seven distinct biological
processes. Most of these proteins are involved in energy metabolism and
many have been found to be dysregulated in previous proteomic studies of
post-mortem brain tissues from schizophrenia patients. Finally, addition
of the antipsychotic clozapine to MK-801 treated oligodendrocyte
cultures resulted in changes in the levels of 45 proteins and treatment
with clozapine alone altered 122 proteins and many of these showed
opposite changes to the MK-801 effects. Therefore, these proteins and
the associated energy metabolism pathways should be explored as
potential biomarkers of antipsychotic efficacy. In conclusion, MK-801
treatment of oligodendrocytes may provide a useful model for testing the
efficacy of novel treatment approaches.
