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Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope
Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancre...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875452/ https://www.ncbi.nlm.nih.gov/pubmed/35216375 http://dx.doi.org/10.3390/ijms23042258 |
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author | Lindenau, Kristen L. Barr, Jeffrey L. Higgins, Christopher R. Sporici, Kevin T. Brailoiu, Eugen Brailoiu, Gabriela C. |
author_facet | Lindenau, Kristen L. Barr, Jeffrey L. Higgins, Christopher R. Sporici, Kevin T. Brailoiu, Eugen Brailoiu, Gabriela C. |
author_sort | Lindenau, Kristen L. |
collection | PubMed |
description | Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancreas and brain, is activated by medium- to long-chain fatty acids. Despite some beneficial effects on cognition, the effects of n-3 PUFAs on the blood–brain barrier (BBB) are not clearly understood. We examined the effects of FFA1 activation on BBB permeability in vitro, using rat brain microvascular endothelial cells (RBMVEC), and in vivo, by assessing Evans Blue extravasation and by performing live imaging of brain microcirculation in adult rats. AMG837, a synthetic FFA1 agonist, produced a dose-dependent decrease in RBMVEC monolayer resistance assessed with Electric Cell–Substrate Impedance Sensing (ECIS); the effect was attenuated by the FFA1 antagonist, GW1100. Immunofluorescence studies revealed that AMG837 produced a disruption in tight and adherens junction proteins. AMG837 increased Evans Blue content in the rat brain in a dose-dependent manner. Live imaging studies of rat brain microcirculation with miniaturized fluorescence microscopy (miniscope) showed that AMG837 increased extravasation of sodium fluorescein. Taken together, our results demonstrate that FFA1 receptor activation reduced RBMVEC barrier function and produced a transient increase in BBB permeability. |
format | Online Article Text |
id | pubmed-8875452 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88754522022-02-26 Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope Lindenau, Kristen L. Barr, Jeffrey L. Higgins, Christopher R. Sporici, Kevin T. Brailoiu, Eugen Brailoiu, Gabriela C. Int J Mol Sci Article Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancreas and brain, is activated by medium- to long-chain fatty acids. Despite some beneficial effects on cognition, the effects of n-3 PUFAs on the blood–brain barrier (BBB) are not clearly understood. We examined the effects of FFA1 activation on BBB permeability in vitro, using rat brain microvascular endothelial cells (RBMVEC), and in vivo, by assessing Evans Blue extravasation and by performing live imaging of brain microcirculation in adult rats. AMG837, a synthetic FFA1 agonist, produced a dose-dependent decrease in RBMVEC monolayer resistance assessed with Electric Cell–Substrate Impedance Sensing (ECIS); the effect was attenuated by the FFA1 antagonist, GW1100. Immunofluorescence studies revealed that AMG837 produced a disruption in tight and adherens junction proteins. AMG837 increased Evans Blue content in the rat brain in a dose-dependent manner. Live imaging studies of rat brain microcirculation with miniaturized fluorescence microscopy (miniscope) showed that AMG837 increased extravasation of sodium fluorescein. Taken together, our results demonstrate that FFA1 receptor activation reduced RBMVEC barrier function and produced a transient increase in BBB permeability. MDPI 2022-02-18 /pmc/articles/PMC8875452/ /pubmed/35216375 http://dx.doi.org/10.3390/ijms23042258 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lindenau, Kristen L. Barr, Jeffrey L. Higgins, Christopher R. Sporici, Kevin T. Brailoiu, Eugen Brailoiu, Gabriela C. Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope |
title | Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope |
title_full | Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope |
title_fullStr | Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope |
title_full_unstemmed | Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope |
title_short | Blood–Brain Barrier Disruption Mediated by FFA1 Receptor—Evidence Using Miniscope |
title_sort | blood–brain barrier disruption mediated by ffa1 receptor—evidence using miniscope |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875452/ https://www.ncbi.nlm.nih.gov/pubmed/35216375 http://dx.doi.org/10.3390/ijms23042258 |
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