Oligodendrocyte pathophysiology: a new view of schizophrenia

A recent focus of schizophrenia research is disruption of white-matter integrity as a key facet of this complex disorder. This was spurred, partly, by new imaging modalities, magnetic transfer imaging and diffusion tensor imaging, which showed differences in white-matter integrity and tract coherence in persons with schizophrenia compared to controls. Oligodendrocytes, in particular, have been the subject of increased study after gene microarray analyses revealed that six myelin-related genes specific to oligodendrocytes have decreased expression levels in schizophrenia. Oligodendrocytes have also been shown to be decreased in number in the superior frontal gyrus of subjects with schizophrenia. The MAG knockout mouse, missing a myelin-related gene linked to schizophrenia, may prove to be a useful animal model for the dysmyelination observed in the human disease. Studies currently ongoing on this model have found changes in dendritic branching patterns of pyramidal cells in layer III of the prefrontal cortex. Further characterization of the pathology in these mice is underway.