RT Journal Article
SR Electronic
T1 The impact of α-synuclein aggregates on blood-brain barrier integrity in the presence of neurovascular unit cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.08.18.504449
DO 10.1101/2022.08.18.504449
A1 Hamdam Hourfar
A1 Farhang Aliakbari
A1 Shabboo Rahimi Aqdam
A1 Zahra Nayeri
A1 Hassan Bardania
A1 Daniel E. Otzen
A1 Dina Morshedi
YR 2022
UL http://biorxiv.org/content/early/2022/08/19/2022.08.18.504449.abstract
AB The role of the blood-brain barrier (BBB) is to control trafficking of biomolecules and protect the brain. This function can be compromised by pathological conditions. Parkinson’s disease (PD) is characterized by the accumulation of α-synuclein aggregates (αSN-AGs) such as oligomers and fibrils, which contribute to disease progression and severity. Here we study how αSN-AGs affect the BBB in in vitro co-culturing models consisting of human brain endothelial hCMEC/D3 cells alone and co-cultured with astrocytes and neurons/glial cells. When cultivated on their own, hCMEC/D3 cells were compromised by αSN-AGs, which decreased cellular viability, mitochondrial membrane potential, wound healing activity, TEER and permeability parameters, as well as increased the levels of ROS and NO. Co-culturing of these cells with activated microglia also increased BBB impairment according to TEER and systemic immune cell transmigration assays. In contrast, hCMEC/D3 cells co-cultured with astrocytes or dopaminergic neurons or simultaneously treated with their conditioned media showed increased resistance against αSN-AGs. Our work demonstrates the complex relationship between members of the neurovascular unit (NVU) (perivascular astrocytes, neurons, microglia, and endothelial cells), αSN-AGs and BBB.Competing Interest StatementThe authors have declared no competing interest.