RIFAMPICIN SUPPRESSES ALPHA-SYNUCLEIN INDUCED MICROGLIAL ACTIVATION AND IMPROVE NEURON SURVIVAL AGAINST INFLAMMATION

RITA RAISMAN-VOZARI; LEONARDO ACUÑA; SABAH HAMADAT; NATALIA CORBALÁN; GONZÁLEZ LIZÁRRAGA, F.; JEREMY ROCCA; DULCE PAPY- GARCIA; PATRICK MICHEL; ROSANA CHEHÍN; JULIA SEPÚLVEDA

Congreso; Glia Meeting; 2017

Objectives: Microglial cells are the resident immune cells of the brain parenchyma. Sustained activation of microglia is known to play a role in the progression of neurodegenerative diseases such as Parkinson?s disease (PD). It has been suggested that the modulation of microglial activation could prevent neuronal demise and thus the progression of neurodegeneration. Based on clinical studies in the context of infectious diseases where Rifampicin seems to protect patients from neurodegeneration, we hypothesize that Rifampicin, could exert a neuroprotective effect by suppressing microglial activation induced by endogenous pro-inflammatory mediators, such as alpha-synuclein aggregates (ASa).Methods: Primary microglial cells purified from post-natal day 1 C57BL/6J mouse pup brains were pre-treated or not with Rifampicin, then challenged with ASa and incubated for 24 h. Conditioned media were collected to perform ELISA assays to measure cytokine levels (TNF-α, IL-1, IL-6). Adherent cells were either fixed for immunostaining procedures or lysed for western blot assays. The modulatory effect of drugs on cell proliferation was also followed by thymidine incorporation. Cortical neurons purified from C57BL/6J mouse embryos were challenged to microglial induced conditioned media. The viability was measured using CCK-8 and LDH releaseResults: Rifampicin readily reduced prototypical markers of inflammation induced by ASa such as (i) Iba-1 expression, (ii) TNF-α and IL-6 production and release, (iii) morphological changes, and (iv) cell proliferation, by blocking PI3K/pAKT signaling pathway, (v) neuron survival.Conclusion: Globally, our results suggest that Rifampicin inhibits microglial activation induced by ASa. We thus propose that Rifampicin could be used as a novel treatment for neurodegenerative diseases such as PD.