METABOLIC LIPOTOXICITY-INDUCED NEUROINFLAMMATION: POTENTIAL ROLE OF GLIAL CELLS INTERACTION VIA EXTRACELLULAR VESICLES

VINUESA A; MELINA BELLOTTO; BENTIVEGNA M; GREGOSA, AMAL; POMILIO C; PRESA, JESSICA; BEAUQUIS J; FLAVIA EUGENIA SARAVIA

Congreso; Reunion Anual de la Sociedad Argentina de Investigacion Clinica; 2020

Obesity and related metabolic disorders are important risk factorsfor brain aging, promoting alterations in the plasticity of limbic structuressuch as the hippocampus. Among the underlying mechanisms,chronic inflammation and insulin resistance are crucial factors, alsoassociated with alterations of sphingolipid metabolism. Taking thisinto account, we intend to study mechanisms associated with theimpact of metabolic disturbances on the brain. We aim to assessthe inflammatory response induced by a lipotoxic context and thecommunication between glial cells mediated by the release of extracellularvesicles (EVs) as vehicles of damage propagation.We previously found that C57BL/6 mice exposed to a high fat diet(HFD) presented neuroinflammation, decreased neurogenesis andstructural synaptic alterations, together with spatial memory impairment.To assess potential mechanisms involved, we used anin vitro approach emulating the lipotoxic context with the saturatedfatty acid palmitate (PA). Microglial cultures exposed to PA showeda pro-inflammatory profile and, after purification of EVs from theconditioned media (CM), we found that exosomes altered dendriticspine morphology of hippocampal neurons. Here, we show that inthe presence of ceramide synthesis inhibitor Cambinol, the inducedexpression of IL1β in PA-exposed BV2 microglial cells was diminished(p