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Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link

Diabetic insulin resistance and pro-diabetic diet are reported to increase dementia risk through unknown mechanisms. Emerging evidence suggests that the integrity of blood-brain barrier (BBB) is central to the onset and progression of neurodegeneration and cognitive impairment. Therefore, the curren...

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Autores principales: Takechi, Ryusuke, Lam, Virginie, Brook, Emily, Giles, Corey, Fimognari, Nicholas, Mooranian, Armin, Al-Salami, Hani, Coulson, Stephanie H., Nesbit, Michael, Mamo, John C. L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717019/
https://www.ncbi.nlm.nih.gov/pubmed/29249964
http://dx.doi.org/10.3389/fnagi.2017.00399
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author Takechi, Ryusuke
Lam, Virginie
Brook, Emily
Giles, Corey
Fimognari, Nicholas
Mooranian, Armin
Al-Salami, Hani
Coulson, Stephanie H.
Nesbit, Michael
Mamo, John C. L.
author_facet Takechi, Ryusuke
Lam, Virginie
Brook, Emily
Giles, Corey
Fimognari, Nicholas
Mooranian, Armin
Al-Salami, Hani
Coulson, Stephanie H.
Nesbit, Michael
Mamo, John C. L.
author_sort Takechi, Ryusuke
collection PubMed
description Diabetic insulin resistance and pro-diabetic diet are reported to increase dementia risk through unknown mechanisms. Emerging evidence suggests that the integrity of blood-brain barrier (BBB) is central to the onset and progression of neurodegeneration and cognitive impairment. Therefore, the current study investigated the effect of pro-diabetic diets on cognitive dysfunction in association to BBB integrity and its putative mechanisms. In C57BL/6J mice chronically ingested with a diet enriched in fat and fructose (HFF), Morris Water Maze (MWM) test indicated no significant cognitive decline after 4 weeks of HFF feeding compared to low-fat (LF) fed control. However, at this stage, BBB dysfunction accompanied by heightened neuroinflammation in cortex and hippocampal regions was already evident. After 24 weeks, HFF fed mice showed significantly deteriorated cognitive function concomitant with substantial neurodegeneration, which both showed significant associations with increased BBB permeability. In addition, the data indicated that the loss of BBB tight junctions was significantly associated with heightened inflammation and leukocyte infiltration. The data collectively suggest that in mice maintained on pro-diabetic diet, the dysfunctional BBB associated to inflammation and leukocyte recruitment precedes the neurodegeneration and cognitive decline, possibly indicating causal association.
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spelling pubmed-57170192017-12-15 Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link Takechi, Ryusuke Lam, Virginie Brook, Emily Giles, Corey Fimognari, Nicholas Mooranian, Armin Al-Salami, Hani Coulson, Stephanie H. Nesbit, Michael Mamo, John C. L. Front Aging Neurosci Neuroscience Diabetic insulin resistance and pro-diabetic diet are reported to increase dementia risk through unknown mechanisms. Emerging evidence suggests that the integrity of blood-brain barrier (BBB) is central to the onset and progression of neurodegeneration and cognitive impairment. Therefore, the current study investigated the effect of pro-diabetic diets on cognitive dysfunction in association to BBB integrity and its putative mechanisms. In C57BL/6J mice chronically ingested with a diet enriched in fat and fructose (HFF), Morris Water Maze (MWM) test indicated no significant cognitive decline after 4 weeks of HFF feeding compared to low-fat (LF) fed control. However, at this stage, BBB dysfunction accompanied by heightened neuroinflammation in cortex and hippocampal regions was already evident. After 24 weeks, HFF fed mice showed significantly deteriorated cognitive function concomitant with substantial neurodegeneration, which both showed significant associations with increased BBB permeability. In addition, the data indicated that the loss of BBB tight junctions was significantly associated with heightened inflammation and leukocyte infiltration. The data collectively suggest that in mice maintained on pro-diabetic diet, the dysfunctional BBB associated to inflammation and leukocyte recruitment precedes the neurodegeneration and cognitive decline, possibly indicating causal association. Frontiers Media S.A. 2017-12-01 /pmc/articles/PMC5717019/ /pubmed/29249964 http://dx.doi.org/10.3389/fnagi.2017.00399 Text en Copyright © 2017 Takechi, Lam, Brook, Giles, Fimognari, Mooranian, Al-Salami, Coulson, Nesbit and Mamo. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Takechi, Ryusuke
Lam, Virginie
Brook, Emily
Giles, Corey
Fimognari, Nicholas
Mooranian, Armin
Al-Salami, Hani
Coulson, Stephanie H.
Nesbit, Michael
Mamo, John C. L.
Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link
title Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link
title_full Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link
title_fullStr Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link
title_full_unstemmed Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link
title_short Blood-Brain Barrier Dysfunction Precedes Cognitive Decline and Neurodegeneration in Diabetic Insulin Resistant Mouse Model: An Implication for Causal Link
title_sort blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: an implication for causal link
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717019/
https://www.ncbi.nlm.nih.gov/pubmed/29249964
http://dx.doi.org/10.3389/fnagi.2017.00399
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