title: 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.
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France. Electronic address: pietra.candela@univ-artois.fr.
authors.forename: Pietra
authors.initials: P
authors.lastname: Candela
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Saint-Pol
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Kuntz
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Boucau
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France.
authors.forename: Yordenca
authors.initials: Y
authors.lastname: Lamartiniere
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Gosselet
authors.affiliation: University of Lille Nord de France, Lille, France; Artois University, LBHE, EA 2465, Lens, France; IMPRT-IFR114, Lille, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Fenart
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D002417:Cattle; D018920:Coculture Techniques; D004705:Endocytosis / Q000502:physiology; D042783:Endothelial Cells / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020286:Pericytes / Q000378:metabolism*; D051381:Rats; D011973:Receptors, LDL / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016229:Amyloid beta-Peptides; D011973:Receptors, LDL
keywords: AD; Aβ; BBB; Brain capillary endothelial cells; Brain pericytes; LRP1