Blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: An implication for causal link
© 2017 Takechi, Lam, Brook, Giles, Fimognari, Mooranian, Al-Salami, Coulson, Nesbit and Mamo. 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...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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Frontiers Research Foundation
2017
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1064567 http://hdl.handle.net/20.500.11937/61794 |
| _version_ | 1848760729310593024 |
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| author | Takechi, Ryu Lam, Virginie Brook, Emily Giles, Corey Fimognari, Nicholas Mooranian, Armin Al-Salami, Hani Coulson, Stephanie Nesbit, Michael Mamo, John |
| author_facet | Takechi, Ryu Lam, Virginie Brook, Emily Giles, Corey Fimognari, Nicholas Mooranian, Armin Al-Salami, Hani Coulson, Stephanie Nesbit, Michael Mamo, John |
| author_sort | Takechi, Ryu |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2017 Takechi, Lam, Brook, Giles, Fimognari, Mooranian, Al-Salami, Coulson, Nesbit and Mamo. 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. |
| first_indexed | 2025-11-14T10:20:24Z |
| format | Journal Article |
| id | curtin-20.500.11937-61794 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:20:24Z |
| publishDate | 2017 |
| publisher | Frontiers Research Foundation |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-617942023-04-19T02:32:33Z Blood-brain barrier dysfunction precedes cognitive decline and neurodegeneration in diabetic insulin resistant mouse model: An implication for causal link Takechi, Ryu Lam, Virginie Brook, Emily Giles, Corey Fimognari, Nicholas Mooranian, Armin Al-Salami, Hani Coulson, Stephanie Nesbit, Michael Mamo, John © 2017 Takechi, Lam, Brook, Giles, Fimognari, Mooranian, Al-Salami, Coulson, Nesbit and Mamo. 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. 2017 Journal Article http://hdl.handle.net/20.500.11937/61794 10.3389/fnagi.2017.00399 http://purl.org/au-research/grants/nhmrc/1064567 http://purl.org/au-research/grants/nhmrc/1106613 http://purl.org/au-research/grants/nhmrc/1122734 http://purl.org/au-research/grants/nhmrc/1036358 http://creativecommons.org/licenses/by/4.0/ Frontiers Research Foundation fulltext |
| spellingShingle | Takechi, Ryu Lam, Virginie Brook, Emily Giles, Corey Fimognari, Nicholas Mooranian, Armin Al-Salami, Hani Coulson, Stephanie Nesbit, Michael Mamo, John 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 |
| url | http://purl.org/au-research/grants/nhmrc/1064567 http://purl.org/au-research/grants/nhmrc/1064567 http://purl.org/au-research/grants/nhmrc/1064567 http://purl.org/au-research/grants/nhmrc/1064567 http://hdl.handle.net/20.500.11937/61794 |