V-105 | ALTERATIONS IN CHOLESTEROL TRAFFICKING IN REACTIVE ASTROCYTES AS A CAUSE OF NEURONAL DYSFUNCTION IN INFLAMMATION

Neural excitability, synaptic transmission and neuron-glia interactions
Author: Joaquín Ezequiel Martini | Email: joaquin.martini@mi.unc.edu.ar

Joaquín E. Martini^1°, Mauricio G. Martin^1°

^1° Departamento de Neurobiología Celular y Molecular, Instituto Ferreyra, INIMEC-CONICET-UNC, Universidad Nacional de Córdoba, Córdoba, Argentina

Cholesterol is essential for the function of most eukaryotic cells as it determines characteristics such as membrane fluidity and permeability and plays an important role in signaling processes. In particular, cholesterol is a major regulator of neuronal function. Since peripheral cholesterol does not cross the blood-brain barrier, neurons depend mainly on cholesterol synthesized by astrocytes, which is exported in the form of ApoE-cholesterol complexes. In recent work in the lab, we demonstrated that aged astrocytes manifest alterations in cholesterol transport, including lysosomal accumulation of cholesterol and altered cholesterol transport to neurons. Using primary cultures of astrocytes treated with proinflammatory cytokines, we found that reactive astrocytes reproduce the alterations observed in ageing and also accumulate high levels of cholesterol in the lysosomal compartment. Furthermore, we observed that treatment with cannabidiol (CBD) reversed the observed alterations. Given that the reduction of neuronal cholesterol has a direct impact on brain function, this study provides relevant information to understand how inflammatory processes, such as infections or neurodegenerative diseases, affect neuronal function and proposes a possible rescue strategy by CBD administration.