Autophagy modulates pro-inflammatory mediators in BV2 microglial cells and rescues both LPS and alpha synuclein-induced neuronal cell death.

CLAUDIO BUSSI; JAVIER PERALTA RAMOS; EMILIA GAVIGLIO; DANIELA ARROYO; JOSE IGNACIO GALLEA; SOLEDAD SOLEJ; PABLO IRIBARREN

Coventry

Congreso; BSCB/BSDB Joint Spring Meeting 2015; 2015

Autophagy is a fundamental cellular homeostatic mechanism, whereby cells autodigest parts of their cytoplasm for removal or turnover. Despite the increasing reports studying the effects of autophagy in the CNS, slightly emphasis is placed on microglial cells.The aim of this study was to evaluate the effects of autophagy on the production of pro-inflammatory mediators by BV2 microglial cells, and on neuronal viability in a co-culture model. Autophagy was induced before or after TLR stimulation by rapamycin or trehalose and blocked by using 3-Methyladenine. Autophagy induction in BV2 cells before LPS or alpha-synuclein stimulation downregulated IL1b, IL-6, TNFa and nitric oxide production.Furthermore, we observed in BV2/N2A co-cultures stimulated with LPS or alpha-synuclein fibers that induction of autophagy in microglial cells rescued LPS and alpha-synuclein-induced neuronal cell death.These results suggest that modulation of microglial cells by autophagy could be an important strategy in the context of neurodegenerative diseases.