| Abstract [eng] |
Cerebrovascular and blood-brain barrier (BBB) dysfunction is observed in early stages of Alzheimer's disease (AD). Studies show that both oxidative stress and inflammation can contribute to BBB impairment but exact mechanisms are unknown. Astrocyte-secreted factors play an important role in maintaining barrier function therefore impairment of these cells in early AD stages may be critical for BBB damage. However, there are no reports on how AD-affected astrocyte-derived extracellular vesicles (EVs) influence brain endothelial cells. Understanding the mechanisms of these EVs may contribute to AD pathogenesis elucidation. In the present study, secreted vesicles from wild type and Familial AD mutations-affected astrocytes (WT-EVs and 3Tg-EVs respectively) were characterized by size, morphology and biomarkers specific to exosomes and microvesicles. WT-EVs reduce the expression of pro-inflammatory IFNβ whereas 3Tg-EVs reduce anti-inflammatory SOCS1 in brain endothelium (hCMEC/D3). Also the expression of these genes is partially regulated by PI3K/Akt signaling pathway. In oxidative stress studies, pre-treatment of WT-EVs, but not 3Tg-EVs, reduces tert-butyl hydroxyperoxide-induced mitochondrial reactive oxygen species (ROS) production, indepenently of Nrf1/2 signaling, but does not affect intracellular ROS in hCMEC/D3 cells. |
