Accumulating evidence indicates that schizophrenic patients have white matter abnormalities in the brain, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. For example, gene microarray studies showed the downregulation of genes related to oligodendrocyte function and myelination in the brain of patients. There is, however, little information about pharmacological agents that can target oligodendrocytes in the schizophrenic brain. In this study, we examined the effects of Yokukansan (TJ-54), one of the traditional "Kampo" medicines, on the tissue and behaviors of a schizophrenia animal model. Cuprizone (CPZ)-treated mouse was employed, because this is one of the best characterized demyelinating model and is recently recognized as schizophrenia model as well. CPZ is a copper chelator and has been known to specifically damage to the myelin sheath and oligodendrocytes, but not to cause lesions in other cell types in the central nervous system.
In the present study, CPZ-treated mice showed demyelination and behavioral alterations such as prepulse inhibition and cognitive impairments. CPZ-treated mice with TJ-54 administration had significantly less demyelination level judged by MBP immunohistochemistry and improved behaviors in prepulse inhibition and cognitive functions as compared to CPZ-treated mice. These results suggest that TJ-54 may become a drug for schizophrenia through ameliolating oligodendrocyte pathology.