Journal
FRONTIERS IN CARDIOVASCULAR MEDICINE
Volume 6, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2019.00129
Keywords
swine; heart failure; female sex hormones; dementia; brain
Categories
Funding
- Saskatchewan Health Research Foundation Establishment Grant [4522]
- Scottish Rite Charitable Foundation [17114]
- Alzheimer Society Foundation Brant-Haldimand-Norfolk-Hamilton-Halton
- Natural Sciences and Engineering Research Council of Canada [2018-03840]
- National Institutes of Health [R01 HL112998]
- Saskatchewan Research Chair in Alzheimer disease and related dementia - Alzheimer Society of Saskatchewan
- Saskatchewan Research Chair in Alzheimer disease and related dementia - Saskatchewan Health Research Foundation
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Post-menopausal women with heart failure (HF) frequently exhibit cardiogenic dementia. Using a pre-clinical swine model of post-menopausal HF, we recently demonstrated that experimental menopause (ovariectomy; OVX) and HF (6-month cardiac pressure overload/aortic banding; AB) independently altered cerebral vasomotor control and together impaired cognitive function. The purpose of this study was to examine the prefrontal cortex and hippocampus tissues from these animals to assess whether OVX and HF are associated with neurologic alterations that may contribute to cardiogenic dementia. We hypothesized that OVX and HF would independently alter neuronal cell signaling in swine with post-menopausal cardiogenic dementia. Immunoblot analyses revealed OVX was associated with reduced estrogen receptor-a in both brain regions and HF tended to exacerbate OVX-induced deficits in the hippocampus. Further, OVX was associated with a reduction in the ratio of phosphorylated: total Akt and ERK in the hippocampus as well as decreased total Akt and synaptophysin in the prefrontal cortex. In contrast, HF was associated with a trend toward reduced phosphorylated: total ERK in the prefrontal cortex. In addition, HF was associated with decreased beta-amyloid (1-38) in the prefrontal cortex and increased beta-amyloid (1-38) in the hippocampus. Regional brain lipid analysis revealed OVX tended to increase total, saturated, and monounsaturated fatty acid content in the prefrontal cortex, with the greatest magnitude of change occurring in the AB-OVX group. The data from this study suggest that OVX and HF are independently associated with regional-specific neurologic changes in the brain that contribute to the cardiogenic dementia profile in this model. This pre-clinical swine model may be a useful tool for better understanding post-menopausal cardiogenic dementia pathology and developing novel therapies.
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