004 | Cannabidiol (CBD) is able to release abnormal cholesterol accumulation in aged astrocytes.

Cellular and Molecular Neurobiology

Author: Leandro German Allende | Email: lallende@immf.uncor.edu

Leandro G. Allende , Mauricio G. Martin

1° Laboratorio de Neurobiología, Instituto de Investigación Médica Mercedes y Martín Ferreyra (INIMEC-CONICET- UNC), Universidad Nacional de Córdoba, Córdoba, Argentina.

The brain stands out as the body’s most cholesterol-abundant organ, accounting for approximately 25% of the total cholesterol present in the body. Within neurons, cholesterol’s significance is underscored by its pivotal role in facilitating neurite growth, synaptogenesis, and the optimal functioning of both pre and post-synaptic compartments. As a result, precise regulation of cholesterol homeostasis within the brain is imperative to avoid potential imbalances that could significantly impair brain performance.
Prior findings from our research group have strongly suggested a connection between the decline in neuronal cholesterol levels during the aging process and the emergence of cognitive impairments. Given the impermeability of the blood-brain barrier to cholesterol, the maintenance of brain cholesterol equilibrium relies heavily on de novo synthesis, primarily orchestrated by glial cells.
In the scope of this study, we present evidence indicating that the aging process triggers an increase in miR33 levels. This, in turn, instigates a Niemann-Pick phenotype in aging astrocytes, leading to the accumulation of cholesterol within lysosomal compartments. Moreover, utilizing astrocyte-neuron cocultures, we have ascertained that the transfer of cholesterol from astrocytes to neurons becomes compromised in vitro-aged astrocytes and could be improved by cannabinoids.