Abstract
Oligodendrocytes are responsible for myelin sheath formation in axons and are compromised in demyelinating diseases, but no treatment has been established to promote their regeneration. In this study, we utilized next-generation sequencing data to analyze the effect of miconazole and clobetasol—two inducers of myelination—on the transcriptome in mice. We found that sterol regulatory element binding factor (SREBF) was involved in myelination. We then screened for SREBF-activating compounds in silico and found the PPARα agonist fenofibrate. Subsequently, we created a transgenic zebrafish line that expresses mCitrine fluorescent protein in oligodendrocytes, under myelin basic protein promotor control. We administered fenofibrate to this zebrafish and performed in vivo imaging by high content screening, and found increased fluorescence signal in oligodendrocytes. Moreover, administering gemfibrozil, another PPARα agonist, to the zebrafish also resulted in a similar increase. This increase induced by fenofibrate or gemfibrozil was suppressed by simultaneous administration of the SREBF inhibitor fatostatin, suggesting that fenofibrate and gemfibrozil induced myelination via SREBF. This approach enables a high-throughput search for novel myelination drugs.
