Nestorone®, a 19nor‐progesterone derivative boosts remyelination in an animal model of demyelination

Introduction We previously showed that Nestorone® (NES), a synthetic progestin structurally related to progesterone, stimulated remyelination of the corpus callosum in a Cuprizone (CUP) mouse model of demyelination in intact females by promoting replenishment with mature oligodendrocytes (OL) (Glia. 2015;63:104‐117). Here, we further investigated the underlying mechanisms of this promyelinating effect. Methods We explored whether NES, applied subcutaneously through Alzet mini‐osmotic pumps, regulates specific transcription factors involved in oligodendrocyte progenitor cell (OPC) proliferation and their differentiation into mature OL, using RT‐qPCR and Western Blot analysis. Results Our present data show that in comparison to controls, a one‐week treatment with NES, through Alzet mini‐osmotic pumps, enhanced the production of three relevant transcription factor mRNAs encoding Olig2, Myt1, and Sox17. After 3 weeks, NES treatment reversed the effect of CUP on the levels of corresponding Olig2, Myt1, and Sox17 proteins. Moreover, in mice receiving NES + Estradiol (E2) co‐treatment, levels of Olig2, Myt1, and Sox17 proteins did not change as compared to NES alone. Conclusion NES alone or with E2 increased the levels of transcription factors, essential for myelin synthesis.
Schematic view of the first demonstration of the mechanism by which Nestorone® a synthetic progestin structurally related to progesterone stimulates remyelination of the corpus callosum in a mouse model of demyelination, by increasing the levels of transcription factors Olig2, Myt1, and Sox17 proteins, essential for myelin synthesis after one week of treatment.