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dc.contributor.authorMamo, John
dc.contributor.authorLam, Virginie
dc.contributor.authorGiles, Corey
dc.contributor.authorCoulson, Stephanie
dc.contributor.authorFimognari, Nick
dc.contributor.authorMooranian, Armin
dc.contributor.authorAl-Salami, Hani
dc.contributor.authorTakechi, Ryu
dc.date.accessioned2017-03-24T11:53:51Z
dc.date.available2017-03-24T11:53:51Z
dc.date.created2017-03-23T06:59:49Z
dc.date.issued2017
dc.identifier.citationMamo, J. and Lam, V. and Giles, C. and Coulson, S. and Fimognari, N. and Mooranian, A. and Al-Salami, H. et al. 2017. Anti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice. International Journal of Obesity. In Press.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/51539
dc.identifier.doi10.1038/ijo.2017.57
dc.description.abstract

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.

dc.titleAnti-hypertensive agents do not prevent blood-brain barrier dysfunction and cognitive deficits in dietary-induced obese mice
dc.typeJournal Article
dcterms.source.issn1476-5497
dcterms.source.titleInternational Journal of Obesity
curtin.departmentSchool of Public Health
curtin.accessStatusFulltext not available


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