PROGESTINS AS ANTI-INFLAMMATORY FACTORS IN NEUROLOGICAL DISORDERS

MEYER M.; GONZALEZ DENISELLE M.C.; GARAY L.; GARGIULO-MONACHELLI G.; DE NICOLA A.F.; LARA A.

Buenos Aires

Simposio; 2ND. FALAN CONGRESS; 2016

IBRO

An increasing number of reports supports that progesterone provides neuroprotection against CNS diseases. In the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), progesterone treatment decreased cell infiltration, changed microglia phenotype and reduced the proinflammatory mediators TNFalpha, TLR4 and iNOS in the spinal cord. Concomitantly, progesterone increased myelin proteins and oligodendrocyte progenitors. To elucidate possible mediators of these effects, we analyzed the mRNA of neurosteroidogenic enzymes, considering that locally synthesized steroids bring neuroprotection by autocrine/paracrine mechanisms. We found that in EAE mice progesterone treatment restored the mRNA for the steroidogenic acute regulatory protein (Star), voltage-dependent anion channel (VDAC), P450scc (cholesterol side-chain cleavage), 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase and aromatase. We also found that the 18 Kd translocator protein (TSPO), a marker of reactive microgliosis was decreased, consequent with the inhibition of microglia reactivity. EAE mice showed pathological mitochondrial morphology and reduced expression of fission and fusion proteins, parameters restored by progesterone. These data indicate that progesterone neuroprotection include the recovery of neurosteroidodogenesis. In this way, endogenously synthesized neurosteroids may reinforce the anti-inflammatory and promyelinating effects of exogenous progesterone found in MS mice