Prostacyclin promotes oligodendrocyte precursor recruitment and remyelination after spinal cord demyelination |
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| Authors: | C Takahashi R Muramatsu H Fujimura H Mochizuki T Yamashita |
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| Institution: | 1.Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565–0871, Japan;2.Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, Chiyoda, Tokyo 102–0075, Japan;3.Toneyama National Hospital, Toyonaka, Osaka, Japan;4.Department of Neurology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan |
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| Abstract: | Adult oligodendrocyte precursor cells (OPCs) are located adjacent to demyelinated lesion and contribute to myelin repair. The crucial step in remyelination is the migration of OPCs to the demyelinated area; however, the mechanism of OPC migration remains to be fully elucidated. Here we show that prostacyclin (prostaglandin I2, PGI2) promotes OPC migration, thereby promoting remyelination and functional recovery in mice after demyelination induced by injecting lysophosphatidylcholine (LPC) into the spinal cord. Prostacyclin analogs enhanced OPC migration via a protein kinase A (PKA)-dependent mechanism, and prostacyclin synthase expression was increased in the spinal cord after LPC injection. Notably, pharmacological inhibition of prostacyclin receptor (IP receptor) impaired remyelination and motor recovery, whereas the administration of a prostacyclin analog promoted remyelination and motor recovery after LPC injection. Our results suggest that prostacyclin could be a key molecule for facilitating the migration of OPCs that are essential for repairing demyelinated areas, and it may be useful in treating disorders characterized by demyelination. |
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| Keywords: | lysophosphatidylcholine protein kinase A multiple sclerosis |
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