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In vitro discrimination of the role of LRP1 at the BBB cellular level: focus on brain capillary endothelial cells and brain pericytes.

Abstract：

:Several studies have demonstrated that the blood-brain barrier (BBB) (dynamic cellular complex composed by brain capillary endothelial cells (BCECs) and surrounded by astrocytic end feet and pericytes) regulates the exchanges of amyloid β (Aβ) peptide between the blood and the brain. Deregulation of these exchanges seems to be a key trigger for the brain accumulation of Aβ peptide observed in Alzheimer's disease (AD). Whereas the involvement of receptor for advanced glycation end-products in Aβ peptide transcytosis has been demonstrated in our laboratory, low-density lipoprotein receptor's role at the cellular level needs to be clarified. For this, we used an in vitro BBB model that consists of a co-culture of bovine BCECs and rat glial cells. This model has already been used to characterize low-density lipoprotein receptor-related peptide (LRP)'s involvement in the transcytosis of molecules such as tPA and angiopep-2. Our results suggest that Aβ peptide efflux across the BCEC monolayer involves a transcellular transport. However, the experiments with RAP discard an involvement of LRP family members at BCECs level. In contrast, our results show a strong transcriptional expression of LRP1 in pericytes and suggest its implication in Aβ endocytosis. Moreover, the observations of pericytes contraction and local downregulation of LRP1 in response to Aβ treatment opens up perspectives for studying this cell type with respect to Aβ peptide metabolism and AD.

journal_name

Brain Res

journal_title

Brain research

authors

Candela P,Saint-Pol J,Kuntz M,Boucau MC,Lamartiniere Y,Gosselet F,Fenart L

doi

10.1016/j.brainres.2014.10.047

subject

Has Abstract

pub_date

2015-01-12 00:00:00

pages

15-26

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(14)01469-3

journal_volume

1594

pub_type

杂志文章

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