Effect of Amyloid Beta on Cholesterol Metabolism-Correlated microRNAs in Primary Cultured Astrocytes of C57BL/6J Mice: A Focus on CYP46A1 and APOE Genes.

Abstract

Objective: The accumulation of amyloid plaques and disturbance of cholesterol homeostasis are implicated in the pathophysiology of Alzheimer's disease. Apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) are key proteins involved in the efflux and metabolism of excess cholesterol, and small non-coding RNAs (miRNAs), can help to regulate the expression of the genes encoding these proteins. The aim of the present study was to investigate the alterations in the expression of APOE and CYP46A1 genes, as well as their respective regulatory miRNAs, in astrocytes treated with amyloid beta (Aβ).

Materials and methods: In this experimental study, isolated astrocyte cells were cultured and treated with Aβ for 24 hours. Changes in the expression of APOE and CYP46A1 genes, as well as their regulating miRNAs, were assessed using the realtime polymerase chain reaction (PCR) technique.

Results: The expression of APOE and CYP46A1 genes increased with Aβ treatment. MiR-33a-5p, as the negative regulator of the APOE gene exhibited significant decrease. Additionally, miR-let-7a-5p, as the positive regulator of the APOE gene, showed an increase in the Aβ treated group. Moreover, miR-98-5p, as the negative regulator of the CYP46A1 gene, showed a half-fold decrease. While, miR-27a-3p as the positive regulator of the CYP46A1 gene, increased significantly with Aβ treatment.

Conclusion: Alterations in the expression of APOE and CYP46A1 genes, as well as the expression of miRNAs regulating these genes, in astrocytes treated with Aβ suggests that the cell is attempting to modify the regulatory pathways of cholesterol homeostasis in the brain under pathological conditions, such as Alzheimer's disease.