Efficacy of the selective progesterone receptor agonist Nestorone for chronic experimental autoimmune encephalomyelitis

GARAY L.; GONZALEZ DENISELLE, M.C.; SITRUK-WARE REGINE; GUENNOUN R; MICHAEL SCHUMACHER; ALEJANDRO F. DE NICOLA

JOURNAL OF NEUROIMMUNOLOGY

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014 vol. 276 p. 89 - 97

0165-5728

Progesterone plays a protective role in the experimental autoimmune encephalomyelitis (EAE) model of multiplesclerosis (MS). Besides spinal cord neuropathology,MS patients present a dysfunctional hippocampus. In thiswork we studied the therapeutic effects of the progestin Nestorone in the brain of mice with chronic EAE.Nestorone decreased clinical grade and enhanced motor behavior. In addition, it increased cell proliferationand doublecortin positive neuroblasts in the hippocampus, increased GABAergic interneurons and attenuatedthe number of Iba1+ microglia/macrophages, events possibly linked to enhancement of neurogenesis.Therefore, Nestorone protected against hippocampus abnormalities and improved functional outcomes of EAEmice, suggesting its potential value for MS.© 2014 Elsevier B.V. All rights reserved.1. IntroductionThe most common inflammatory/demyelinating disease of the centralnervous systemismultiple sclerosis (MS). Considered an inflammatorydisease of autoimmune origin, there are also indications thatprimary cytodegeneration may be the initial event in some clinicalforms of MS (McQualter and Bernard, 2007; Trapp and Nave, 2008;Stys et al., 2012; Ellwardt and Zipp, 2014). In this regard, there mightbe intrinsic defects of the oligodendrocytes, with release of myelinproteins and debris that provokes a secondary reaction of the immunesystem (Matute and Perez-Cerda, 2005; Stys et al., 2012).A role of steroid hormones in MS has been substantiated by its genderdifference (women to men ratio about 2.3) and by the decline inrelapse rate