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

VINUESA A; BELLOTTO M; BENTIVEGNA M; GREGOSA A; POMILIO C; PRESA J; BEAUQUIS J; SARAVIA F

Congreso; Reunión de Sociedades de Biociencias 2020; 2020

Sociedad Argentina de Investigación Clínica

Obesity and related metabolic disorders are important risk factors for brain aging, promoting alterations in the plasticity of limbic structures such as the hippocampus. Among the underlying mechanisms, chronic inflammation and insulin resistance are crucial factors, also associated with alterations of sphingolipid metabolism. Taking this into account, we intend to study mechanisms associated with the impact of metabolic disturbances on the brain. We aim to assess the inflammatory response induced by a lipotoxic context and the communication between glial cells mediated by the release of extracellular vesicles (EVs) as vehicles of damage propagation. We previously found that C57BL/6 mice exposed to a high fat diet (HFD) presented neuroinflammation, decreased neurogenesis and structural synaptic alterations, together with spatial memory impairment. To assess potential mechanisms involved, we used an in vitro approach emulating the lipotoxic context with the saturated fatty acid palmitate (PA). Microglial cultures exposed to PA showed a pro-inflammatory profile and, after purification of EVs from the conditioned media (CM), we found that exosomes altered dendritic spine morphology of hippocampal neurons. Here, we show that in the presence of ceramide synthesis inhibitor Cambinol, the induced expression of IL1β in PA-exposed BV2 microglial cells was diminished (p