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

BUSSI C; PERALTA RAMOS J; GAVIGLIO EA; ARROYO DS; GALLEA JI; CELEJ MS; IRIBARREN P

Coventry

Congreso; British Society for Cell Biology Spring Meeting and at the First UK Autophagy Network Meeting; 2015

School of Life Sciences and The Francis Crick Institute

Autophagy is a fundamental cellular homeostaticmechanism, whereby cells autodigest parts of their cytoplasm for removal orturnover. Despite the increasing reports studying the effects ofautophagy in the CNS, slightly emphasis is placed on microglial cells.The aim of this study was to evaluate the effects ofautophagy on the production of pro-inflammatory mediators by BV2 microglialcells, and on neuronal viability in a co-culture model. Autophagy was induced before or after TLR stimulationby rapamycin or trehalose and blocked by using 3-Methyladenine. Autophagyinduction in BV2 cells before LPS or alpha-synuclein stimulation downregulatedIL1b, IL-6, TNFa and nitric oxide production.Furthermore,we observed in BV2/N2A co-cultures stimulated with LPS or alpha-synucleinfibers that induction of autophagy in microglial cells rescued LPS and alpha-synuclein-inducedneuronal cell death.Theseresults suggest that modulation of microglial cells by autophagy could be animportant strategy in the context of neurodegenerative diseases.