Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice
BACKGROUND: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood-brain barrier (BBB) may play an important role in neurodegene...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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2017
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| Online Access: | http://hdl.handle.net/20.500.11937/51539 |
| _version_ | 1848758723792601088 |
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| author | Mamo, John Lam, Virginie Giles, Corey Coulson, Stephanie Fimognari, Nick Mooranian, Armin Al-Salami, Hani Takechi, Ryu |
| author_facet | Mamo, John Lam, Virginie Giles, Corey Coulson, Stephanie Fimognari, Nick Mooranian, Armin Al-Salami, Hani Takechi, Ryu |
| author_sort | Mamo, John |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | BACKGROUND: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood-brain barrier (BBB) may play an important role in neurodegeneration and cognitive deficits. A number of studies report that elevated blood pressure increases the permeability of BBB. METHODS: In this study, we investigated the effects of anti-hypertensive agents, candesartan or ursodeoxycholic acid (UDCA), on BBB dysfunction and cognitive decline in wild-type mice maintained on high fat and fructose (HFF) diet for 24 weeks. RESULTS: In HFF-fed mice, significantly increased body weight with elevated blood pressure, plasma insulin and glucose compared to mice fed with low-fat control chow was observed. Concomitantly, significant disruption of BBB and cognitive decline were evident in the HFF-fed obese mice. Hypertension was completely prevented by the co-provision of candesartan or UDCA in mice maintained on HFF diet, while only candesartan significantly reduced the body weight compared to HFF-fed mice. Nevertheless, BBB dysfunction and cognitive decline remained unaffected by candesartan or UDCA. CONCLUSIONS: These data conclusively indicate that modulation of blood pressure and/or body weight may not be directly associated with BBB dysfunction and cognitive deficits in Western diet-induced obese mice, and hence anti-hypertensive agents may not be effective in preventing BBB disruption and cognitive decline. The findings may provide important mechanistical insights to obesity-associated cognitive decline and its therapy. |
| first_indexed | 2025-11-14T09:48:32Z |
| format | Journal Article |
| id | curtin-20.500.11937-51539 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:48:32Z |
| publishDate | 2017 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-515392017-09-13T15:41:42Z Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice Mamo, John Lam, Virginie Giles, Corey Coulson, Stephanie Fimognari, Nick Mooranian, Armin Al-Salami, Hani Takechi, Ryu BACKGROUND: While vascular risk factors including Western-styled diet and obesity are reported to induce cognitive decline and increase dementia risk, recent reports consistently suggest that compromised integrity of cerebrovascular blood-brain barrier (BBB) may play an important role in neurodegeneration and cognitive deficits. A number of studies report that elevated blood pressure increases the permeability of BBB. METHODS: In this study, we investigated the effects of anti-hypertensive agents, candesartan or ursodeoxycholic acid (UDCA), on BBB dysfunction and cognitive decline in wild-type mice maintained on high fat and fructose (HFF) diet for 24 weeks. RESULTS: In HFF-fed mice, significantly increased body weight with elevated blood pressure, plasma insulin and glucose compared to mice fed with low-fat control chow was observed. Concomitantly, significant disruption of BBB and cognitive decline were evident in the HFF-fed obese mice. Hypertension was completely prevented by the co-provision of candesartan or UDCA in mice maintained on HFF diet, while only candesartan significantly reduced the body weight compared to HFF-fed mice. Nevertheless, BBB dysfunction and cognitive decline remained unaffected by candesartan or UDCA. CONCLUSIONS: These data conclusively indicate that modulation of blood pressure and/or body weight may not be directly associated with BBB dysfunction and cognitive deficits in Western diet-induced obese mice, and hence anti-hypertensive agents may not be effective in preventing BBB disruption and cognitive decline. The findings may provide important mechanistical insights to obesity-associated cognitive decline and its therapy. 2017 Journal Article http://hdl.handle.net/20.500.11937/51539 10.1038/ijo.2017.57 restricted |
| spellingShingle | Mamo, John Lam, Virginie Giles, Corey Coulson, Stephanie Fimognari, Nick Mooranian, Armin Al-Salami, Hani Takechi, Ryu Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| title | Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| title_full | Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| title_fullStr | Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| title_full_unstemmed | Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| title_short | Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| title_sort | anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice |
| url | http://hdl.handle.net/20.500.11937/51539 |