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

Candela, Pietra; Saint-Pol, Julien; Kuntz, Mélanie; Boucau, Marie-Christine; Lamartinière, Yordenca; Gosselet, Fabien; Fénart, Laurence

doi:10.1016/j.brainres.2014.10.047

Cited by 61 publications

(49 citation statements)

References 68 publications

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“…We hypothesized that KB treatment could be associated with a higher clearance of Aβ peptide through the BBB. Thus, the apical-to-basolateral (influx) and basolateral-to-apical (efflux) Aβ 1-40 Cy5 peptide transport across BLECs was assessed as previously described [13,39,44]. For these experiments, we used Aβ 1-40 , since this is the most abundant amyloid peptide found in brain microvessels [45].…”

Section: Kbs Increase Basolateral-to-apical Aβ Peptide Transport Thromentioning

confidence: 99%

“…Forty-eight hours after KB treatments, the apical-to-basolateral and the basolateral-to-apical transport of Aβ 1-40 across BLECs was investigated as previously described [13,44,46] (Briefly, for apical-to-basolateral studies, filters were transferred to new 12-well plates containing 1.5 mL of RH-HSA 0.1% (the receiver solution) per well. In the insert corresponding to the apical compartment, 0.5 mL of RH-HSA 0.1% supplemented with 10 nM Aβ 1-40 Cy5 peptide was added (the donor solution).…”

Section: Amyloid-β ( 1-40 ) Peptide Transport Studiesmentioning

confidence: 99%

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Ketone Bodies Promote Amyloid-β1–40 Clearance in a Human in Vitro Blood–Brain Barrier Model

Versele

Corsi

Fuso

et al. 2020

IJMS

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Alzheimer’s disease (AD) is characterized by the abnormal accumulation of amyloid-β (Aβ) peptides in the brain. The pathological process has not yet been clarified, although dysfunctional transport of Aβ across the blood–brain barrier (BBB) appears to be integral to disease development. At present, no effective therapeutic treatment against AD exists, and the adoption of a ketogenic diet (KD) or ketone body (KB) supplements have been investigated as potential new therapeutic approaches. Despite experimental evidence supporting the hypothesis that KBs reduce the Aβ load in the AD brain, little information is available about the effect of KBs on BBB and their effect on Aβ transport. Therefore, we used a human in vitro BBB model, brain-like endothelial cells (BLECs), to investigate the effect of KBs on the BBB and on Aβ transport. Our results show that KBs do not modify BBB integrity and do not cause toxicity to BLECs. Furthermore, the presence of KBs in the culture media was combined with higher MCT1 and GLUT1 protein levels in BLECs. In addition, KBs significantly enhanced the protein levels of LRP1, P-gp, and PICALM, described to be involved in Aβ clearance. Finally, the combined use of KBs promotes Aβ efflux across the BBB. Inhibition experiments demonstrated the involvement of LRP1 and P-gp in the efflux. This work provides evidence that KBs promote Aβ clearance from the brain to blood in addition to exciting perspectives for studying the use of KBs in therapeutic approaches.

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Section: Kbs Increase Basolateral-to-apical Aβ Peptide Transport Thromentioning

confidence: 99%

Section: Amyloid-β ( 1-40 ) Peptide Transport Studiesmentioning

confidence: 99%

Ketone Bodies Promote Amyloid-β1–40 Clearance in a Human in Vitro Blood–Brain Barrier Model

Versele

Corsi

Fuso

et al. 2020

IJMS

Self Cite

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“…However, there are conflicting studies showing no or little contribution of LRP1 to Aβ clearance across the BBB (5,(17)(18)(19)(20). Due to the lack of appropriate model systems, the role of LRP1 at the BBB and the overall relevance of BBB clearance are insufficiently understood and debated (4,7).…”

Section: Introductionmentioning

confidence: 99%

Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier

Storck¹,

Meister²,

Nahrath³

et al. 2015

Journal of Clinical Investigation

351

285

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“…In vitro models of the microvasculature are new and exciting tools to study its role in disease states such as VCID. Co-culture systems have taught us a lot about the BBB, from permeability studies of drugs [37, 38] to how Aβ crosses the BBB [39]. Little has been published thus far on the applications of synthetic microvessels, as it is a relatively new technique but the potential applications of the model are broad and range from better understanding the BBB, to having a more clear understanding the roles of individual cell types in the neurovascular unit, and eventually understanding the specific role of the microvasculature in certain diseases.…”

Section: The Neurovascular Unit and Cell Culture Modelsmentioning

confidence: 99%

Vascular cognitive impairment: Modeling a critical neurologic disease in vitro and in vivo

Helman

Murphy

2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Background Vascular contributions to cognitive impairment and dementia (VCID) is a complex form of dementia, combining aspects of vascular disease and other forms of dementia, such as Alzheimer’s disease. VCID encompasses a wide spectrum of cerebrovascular-driven cognitive impairment, from mild cognitive impairment to fully developed dementia. This disease state is further complicated by metabolic disorders, such as type 2 diabetes and hypertension, and lifestyle factors, like obesity and high fat diets. Scope of Review This manuscript is meant to both define VCID and review the in vitro and in vivo models of the disease state. This includes in vitro models of the neurovascular unit, models of chronic cerebral hypoperfusion, animals with NOTCH3 mutations as a model of small vessel disease, large animals with cerebral amyloid angiopathy (CAA), and animal models of mixed dementia. Major Conclusions Synthetic microvessels are a promising technique to study the neurovascular unit and canines, despite the cost, are an excellent model to study CAA. While there are several good models of individual aspects of VCID, the heterogeneity of the disease states prevents there from being a model of all aspects of the disease. Therefore, VCID needs to be further defined into disease states that exist within this umbrella term. This includes specific guidelines for stroke counts and stroke locations and further categorization of overlapping cerebrovascular and AD pathologies that contribute to dementia. This will allow for better models and a more thorough understanding of how vascular disease contributes to dementia. General Significance VCID is the second most common form of dementia and is expected to increase in coming years. The heterogeneity of VCID makes it difficult to study, but without better definitions and models, VCID presents a major public health problem for our aging population.

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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

Cited by 61 publications

References 68 publications

Ketone Bodies Promote Amyloid-β1–40 Clearance in a Human in Vitro Blood–Brain Barrier Model

Ketone Bodies Promote Amyloid-β1–40 Clearance in a Human in Vitro Blood–Brain Barrier Model

Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier

Vascular cognitive impairment: Modeling a critical neurologic disease in vitro and in vivo

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