Xiao L et al. (2007) Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. Mol Psychiatry [doi:10.1038/sj.mp.4002064]

Recent structural and neuroimaging studies have reported white matter abnormalities in the brains of patients with schizophrenia, suggesting that oligodendrocytes might be involved in the etiopathology of this condition. To investigate this hypothesis, Xiao et al. studied the response of oligodendrocytes to antipsychotic drugs.

Neural progenitor cells (NPCs) isolated from rat fetuses were treated with a range of antipsychotic drugs, but only quetiapine (in conjunction with other growth factors) increased proliferation of NPCs in neurosphere cultures. Quetiapine also stimulated NPCs to differentiate into oligodendrocytes, through extracellular signal-related kinases, and increased myelin basic protein expression in cortical aggregate cultures in a dose-dependent manner (P <0.0001). To test the effect of quetiapine on cortical myelin breakdown in vivo, 8-week-old mice were fed 0.2% cuprizone, which causes myelin breakdown by specifically damaging oligodendrocytes, for 4 weeks and were subsequently tested on a Y-maze task. Treatment of mice with quetiapine beginning 1 week before introduction of cuprizone significantly prevented behavioral changes compared with the control group (P <0.05).

These findings suggest a mechanism for the antipsychotic action of quetiapine that targets oligodendrocytes. Furthermore, the data help to establish a role for oligodendrocytes in the etiopathology of schizophrenia, although it is not clear whether oligodendrocytes can also be implicated in other neuropsychiatric disorders involving myelination development problems. The authors suggest that promyelinating treatment could be a viable therapeutic approach for schizophrenia.