Cellular and Molecular Neurobiology
Author: Gabriel Cataldi | email: gcataldi@immf.uncor.edu
Gabriel E. Cataldi 1°, Mauricio G. Martin 1°
1° Instituto Ferreyra, INIMEC-CONICET-UNC, Universidad Nacional de Córdoba, Córdoba, Argentina.
CYP46 carries out the hydroxylation of cholesterol to 24(S)HOC, which is the main mechanism of cholesterol elimination from the brain. CYP46 has been mainly reported in neuronal populations, however, in cases of brain damage such as traumatic brain injury or Alzheimers disease CYP46 increases its expression in astrocytes. However, the role that CYP46 would play in astrocytes in pathological conditions is unknown. We found that CYP46 levels are greatly increased in reactive astrocytes treated with lipopolysaccharide (LPS) and IL-6. Accordingly, IL-6 was able to increase APP synthesis in primary astrocytes. Providing a link between CYP46 and APP, our results show that 24(S)HOC-treated primary cortical astrocytes showed a marked increase in APP levels compared to control cells. Our data indicate that 24(S)HOC appears to exert its role through epigenetic mechanisms. We propose that under a proinflammatrory context, as for example a microbial infection in the brain, 24(S)HOC would mediate the production of APP and A? in astrocytes to face the aggression but on the other side it would predispose to Alzheimer’s disease.