title: Prostacyclin promotes oligodendrocyte precursor recruitment and remyelination after spinal cord demyelination.
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.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Takahashi
authors.forename: R
authors.initials: R
authors.lastname: Muramatsu
authors.forename: H
authors.initials: H
authors.lastname: Fujimura
authors.forename: H
authors.initials: H
authors.lastname: Mochizuki
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003711:Demyelinating Diseases / Q000473:pathology* / Q000503:physiopathology; D011464:Epoprostenol / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011494:Protein Kinases / Q000378:metabolism; D044006:Receptors, Epoprostenol / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D013234:Stem Cells / Q000473:pathology*
chemical_list: D044006:Receptors, Epoprostenol; D011464:Epoprostenol; D000242:Cyclic AMP; D011494:Protein Kinases
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