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Animal Models

Antihypertensive agents do not prevent blood–brain barrier dysfunction and cognitive deficits in dietary-induced obese mice

International Journal of Obesity volume 41, pages 926–934 (2017)Cite this article

Subjects

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 have 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 antihypertensive 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 with 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 coprovision of candesartan or UDCA in mice maintained on HFF diet, while only candesartan significantly reduced the body weight compared with 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 antihypertensive 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.

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Acknowledgements

We thank Curtin Health Innovation Research Institute for its technical and infrastructure support. We would also like to acknowledge Dr Mina Elahy for her assistance in sample and data collection. The study was financially supported by Western Australian Department of Health, Australian National Health and Medical Research Council Project Grants, Alzheimer’s Australia Dementia Research Foundation Project Grants and Curtin University Research Support Funds.

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Authors and Affiliations

  1. Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia

    J C L Mamo, V Lam, C Giles, S H Coulson, N Fimognari, A Mooranian, H Al-Salami & R Takechi

  2. School of Public Health, Faculty of Health Sciences, Curtin University, Perth, WA, Australia

    J C L Mamo, V Lam, C Giles, S H Coulson, N Fimognari & R Takechi

  3. School of Pharmacy, Faculty of Health Sciences, Curtin University, Perth, WA, Australia

    A Mooranian & H Al-Salami

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  1. J C L Mamo
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Correspondence to R Takechi.

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Mamo, J., Lam, V., Giles, C. et al. Antihypertensive agents do not prevent blood–brain barrier dysfunction and cognitive deficits in dietary-induced obese mice. Int J Obes 41, 926–934 (2017). https://doi.org/10.1038/ijo.2017.57

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