Progesterone Down-Regulates Spinal Cord Inflammatory Mediators And Increases Myelination in Experimental Autoimmune Encephalomyelitis.

GARAY L; GONZALEZ DENISELLE MC; BROCCA E; LIMA A; ROIG P; DE NICOLA A. F.

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2012 p. 40 - 50

0306-4522

In mice with experimental autoimmune encephalomyelitis (EAE) pretreatment with progesterone improves clinical signs and decreases the loss of myelin basic protein (MBP) and proteolipid protein (PLP) measured by immunohistochemistry and in situ hybridization. Presently, we analyzed if progesterone effects involved decreased transcription of local inflammatory mediators and increased transcription of myelin proteins and myelin transcription factors in the spinal cord. Mice were divided into controls, EAE and EAE receiving progesterone (100 mg implant) 7 days before EAE induction. Tissues were collected on day 17 post-immunization. Real time PCR technology demonstrated that progesterone blocked the EAE-induced increase of the proinflammatory mediators tumor necrosis factor alpha (TNFa) and its receptor TNFR1, the microglial marker CD11b and toll-like receptor 4 (TLR4) mRNAs, and increased mRNA expression of PLP and MBP, the myelin transcription factors Nkx2.2 and Olig1 and enhanced CC1+ oligodendrocyte density respect of untreated EAE mice. Immunocytochemistry demonstrated decreased Iba1+ microglial cells. Confocal microcoscopy demonstrated that TNFa.colocalized with glial-fibrillary acidic protein+ astrocytes and OX-42 + microglial cells. Therefore, improvement of clinical signs of EAE by progesterone is explained by decreased inflammatory glial reactivity and increased myelination. Data suggest that progesterone neuroprotection involves the modulation of transcriptional events in the spinal cord of EAE mice.