Quetiapine promotes oligodendroglial process outgrowth and membrane expansion by orchestrating the effect of GPR17

Oligodendroglial lineage cells go through a series of morphological changes prior to myelination.Sufficient cell process outgrowth and mem brane expansion are required to meet the needs of axon-wrapping and myelin segment formation,but which are hard to achieve maldevelopment and remyelination.Quetiapine,an atypical antipsychotic drug,has been proved to promote oligodendrocyte(OL)differentiation and(re)myelination,pending detailed effects and regulatory mechanism.In present study,we showed that quetiapine promoted OL differentiation and myelin segment formation in a short period of treatment,enhanced OL processes outgrowth and membrane expansion,and provided detail evidence that quetiapine relocated nuclear transcription factor Olig1 to cytosol,in which highly correlating with OL morphological transformation.To uncover the underlying mechanism,informatics analyses,including docking and MD studies,were executed.GPR17 was one of the most likely candidates.GPR17 is restricted to oligodendroglial lineage cells in an up-and-down expression pattern and acts as a developmental control timer.