CONICET | Buscador de Institutos y Recursos Humanos

Progesterone treatment of mice with experimentalautoimmune encephalomyelitis has shown beneficial effects inthe spinal cord according to enhanced clinical, myelin and neuronal-related parameters. In the present work, we report progesteroneeffects in a model of primary demyelination induced bythe intraspinal injection of lysophospatidylcholine (LPC).C57Bl6 adult male mice remained steroid-untreated or receiveda single 100 mg progesterone implant, which increased circulatingsteroid levels to those of mouse pregnancy. Seven daysafterwards mice received a single injection of 1% LPC into thedorsal funiculus of the spinal cord. A week after, anesthetizedmice were perfused and paraffin embedded sections of thespinal cord stained for total myelin using Luxol Fast Blue (LFB)histochemistry, for myelin basic protein (MBP) immunohistochemistryand for determination of OX-42 microglia/macrophages.Cryostat sections were also prepared and stained foroligodendrocyte precursors (NG2 cells) and mature oligodendrocytes(CC1 cells). A third batch of spinal cords was preparedfor analysis of the microglial marker CD11b mRNA usingqPCR. Results showed that progesterone pretreatment of LPCinjectedmice decreased by 50% the area of demyelination,evaluated by either LFB staining or MBP immunostaining, increasedthe density of NG2 cells and of mature, CC1 oligodendrocytesand decreased the number of OX-42 cells, respectof steroid-untreated LPC mice. CD11b mRNA was hyperexpressedin LPC-treated mice, but significantly reduced inLPC-mice receiving progesterone. These results indicated thatprogesterone antagonized LPC injury, an effect involving (a)increased myelination; (b) stimulation of oligodendrocyte precursorsand mature oligodendrocytes, and (c) attenuation of themicroglial/macrophage response. Thus, use of a focal demyelinationmodel suggests that progesterone exerts promyelinatingand anti-inflammatory effects at the spinal cord level.