Amyloid Beta 25 –35 induces blood-brain barrier disruption in vitro

AbstractThe amyloid β-peptide (Aβ) is transported across the blood-brain barrier (BBB) by binding with the receptor for advanced glycation end products (RAGE). Previously, we demonstrated that the Aβ fraction 25–35 (Aβ25 –35) increases RAGE expression in the rat hippocampus, likely contributing to its neurotoxic effects. However, it is still debated if the interaction of A β with RAGE compromises the BBB function in Alzheimer’ disease (AD). Here, we evaluated the effects of Aβ25 –35 in an established in vitro model of the BBB. Rat brain microvascular endothelial cells (rBMVECs) were treated with 20  μM active Aβ25 –35 or the inactive A β35 –25 (control), for 24  h. Exposure to Aβ25 –35 significantly decreased cell viability, increased cellular necrosis, and increased the production of reactive oxygen species (ROS), which triggered a decrease in the enzyme glutathione peroxidase when compared to the control condition. A β25 –35 also increased BBB permeability by altering the expression of tight junction proteins (decreasing zonula occludens-1 and increasing occludin). A β25 –35 induced monolayer disruption and cellular disarrangement of the BBB, with RAGE being highly expressed in the zones of disarrangement. Together, these data suggest that A β25 –35-induces toxicity by compromising the functionality and integrity of the BBB in vitro.Graphical abstractA β25-35 induces BBB dysfunctionin vitro, wich is likely mediated by OS and ultimately le...

Source: Metabolic Brain Disease - July 1, 2019 Category: Neurology Source Type: research