PROGESTERONE ATTENUATES DEMYELINATION AND MICROGLIAL REACTION IN THE LYSOLECITHIN-INJURED SPINAL CORD

GARAY L.; TUENGLER V.; GONZALEZ DENISSELLE, MC; LIMA A.; ROIG P. ; DE NICOLA A.F.

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 192 p. 588 - 597

0306-4522

Progesterone treatment of mice with experimental autoimmune encephalomyelitis has shown beneficial effects in the spinal cord according to enhanced clinical, myelin and neuronal-related parameters. In the present work, we report progesterone effects in a model of primary demyelination induced by the intraspinal injection of lysophospatidylcholine (LPC).  C57Bl6 adult male mice remained steroid-untreated or received a single 100 mg progesterone implant, which increased circulating steroid levels to those of mouse pregnancy. Seven days afterwards mice received a single injection of 1% LPC into the dorsal funiculus of the spinal cord. A week after, anesthetized mice were perfused and paraffin embedded sections of the spinal cord stained for total myelin using Luxol Fast Blue (LFB) histochemistry, and for myelin basic protein (MBP) immunohistochemistry. Cryostat sections were also prepared and stained for oligodendrocyte precursors (NG2+ cells) and mature oligodendrocytes (CC1+ cells). A third batch of spinal cords was prepared for analysis of the microglial marker CD11b mRNA using qPCR. Results showed that progesterone pretreatment of LPC-injected mice decreased by 50% the area of demyelination, evaluated by either LFB staining or MBP immunostaining and increased the density of NG2+ cells and of mature, CC1+ oligodendrocytes respect of steroid-untreated LPC mice. CD11b mRNA was hyperexpressed in LPC-treated mice, but significantly reduced in LPC-mice receiving progesterone. These results indicated that progesterone antagonized LPC injury, an effect involving (a) increased myelination; (b) stimulation of oligodendrocyte precursors and mature oligodendrocytes, and (c) attenuation of microglial activation. Thus, use of a focal demyelination model suggests that the promyelinating and anti-inflammatory effects of progesterone may directly occur at the spinal cord level.