Impact of ceramide synthesis inhibition on glial activation and extracellular vesicles liberation in an experimental Alzheimer’s disease model.

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

Mar del Plata

Congreso; REUNIÓN CONJUNTA SAIC SAB AAFE AACYTAL 2023; 2023

Sociedad Argentina de Investigación Clínica (SAIC)

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and the leading cause of dementia. One of its hallmarks is the deposition of amyloid β (Aβ) in the brain. Also, high levels of ceramides in plasma and CSF of AD patients could have a pro-inflammatory role. Recently, there has been growing interest in the role of small extracellular vesicles (SEVs) in AD. Previously, we reported that SEVs propagate inflammatory stimuli from microglia to neurons. Ceramides are important components of SEVs and can regulate their production. Here, we aimed to study 1) the effects of inhibiting ceramide synthesis in an AD murine model; 2) the impact of Aβ and palmitate (PA), a ceramide precursor, on glial activation and communication via SEVs and the regulation by ceramide synthesis.In vivo, we administered Myriocin (1 mg/Kg/dose, 9 doses, 3 weeks), an SPT inhibitor, to 8-m-old PDAPPJ20 transgenic mice. We found that transgenic mice performed worse than non-transgenic controls in short-term memory tests (ANOVA, P