Progesterone down-regulates spinal cord inflammatory mediators and increases myelination in experimental autoimmune encephalomyelitis.

LAURA I. GARAY; MARÍA C. GONZÁLEZ DENISELLE; MARÍA E. BROCCA; ANALÍA LIMA; PAULINA ROIG; ALEJANDRO DE NICOLA

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 226 p. 40 - 50

0306-4522

Abstract—In mice with experimental autoimmune encephalomyelitis(EAE) pretreatment with progesterone improvesclinical signs and decreases the loss of myelin basic protein(MBP) and proteolipid protein (PLP) measured by immunohistochemistryand in situ hybridization. Presently, weanalyzed if progesterone effects in the spinal cord of EAEmice involved the decreased transcription of local inflammatorymediators and the increased transcription of myelinproteins and myelin transcription factors. C57Bl/6 femalemice 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. Realtime PCR technology demonstrated that progesteroneblocked the EAE-induced increase of the proinflammatorymediators tumor necrosis factor alpha (TNFa) and its receptorTNFR1, the microglial marker CD11b and toll-like receptor4 (TLR4) mRNAs, and increased mRNA expression ofPLP and MBP, the myelin transcription factors NKx2.2 andOlig1 and enhanced CC1 + oligodendrocyte density respectof untreated EAE mice. Immunocytochemistry demonstrateddecreased Iba1+ microglial cells. Confocal microscopydemonstrated that TNFa colocalized with glialfibrillaryacidic protein+ astrocytes and OX-42+ microglialcells. Therefore, progesterone treatment improved theclinical signs of EAE, decreased inflammatory glialreactivity and increased myelination. Data suggest thatprogesterone neuroprotection involves the modulation oftranscriptional events in the spinal cord of EAE mice. 2012 IBRO. Published by Elsevier Ltd. All rights reserved.