PROGESTINS AS ANTI-INFLAMMATORY FACTORS IN NEUROLOGICAL DISORDERS.

MEYER MARIA; GARAY LAURA I; ALEJANDRO F. DE NICOLA; CLAUDIA GONZALEZ DENISELLE

Buenos Aires

Congreso; In Federation of Latin American and Caribbean Neuroscience Societies (FALAN); 2016

Symposia : Neuroesteroids, cardioesteroids and oxidative cell signalling astarget in neuroinflammation and possible role in neurodegenerative disease Progestins asanti-inflammatory factors in neurological disorders. Laura I. Garay, Maria Meyer, Maria ClaudiaGonzalez Deniselle and Alejandro F. De Nicola. Laboratory ofNeuroendocrine Biochemistry, Instituto de Biologia y MedicinaExperimental-CONICET, Vta. De Obligado 2490, 1428Buenos Aires, Argentina.  Progesterone exerts neuroprotective effects in severalCNS diseases. These properties are additional to their reproductive functions.In murine experimental autoimmune encephalomyelitis(EAE), a model of multiple sclerosis (MS), progesterone treatment decreased cell infiltration, changed the microglia phenotype and reducedthe expression of the proinflammatory factors and enzymes TNFalpha, TLR4, COX2 andiNOS. Concomitantly, there was increased expression of myelin central proteins andoligodendrocyte progenitors. To elucidate mediators of these effects, weanalyzed the expression of neurosteroidogenic enzymes, because locally synthesizedneurosteroids play an autocrine/paracrine neuroprotective role. We found thatprogesterone-treatment of EAE mice restored the mRNA levels for thesteroidogenic acute regulatory protein (Star), voltage-dependent anion channel(VDAC), P450scc (cholesterol side-chain cleavage), 5alpha-reductase, 3alpha-hydroxysteroiddehydrogenase (3alpha-HSD) and aromatase, whereas levels of 3beta-hydroxysteroiddehydrogenase (3beta-HSD) showed a large intra-group variance. We also foundthat the 18 Kd translocator protein (TSPO), a marker of reactive microgliosis wasdecreased, consequent with the inhibition of microglia reactivity. EAE mice showedpathological mitochondrial morphology and reduced expression of fission andfusion proteins, parameters restored by progesterone treatment We hypothesized thatprogesterone protective effects on mitochondrial and endoplasmic reticulum mayallow the recovery of neurosteroidodogenesis. In this way, endogenouslysynthesized neurosteroids may reinforce the beneficial effects of exogenousprogesterone shown in MS mice.