Abstract WP418: Mineralocorticoid Receptor Signaling is Associated With Neuroinflammation and Changes in Cognitive Function in Angiotensin II-Induced Hypertension

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Introduction: Mineralocorticoid receptor (MR) activation facilitates hypertension-associated cerebral artery dysfunction and reduced perfusion that may increase the risk for vascular dementia.Hypothesis: Angiotensin II (AngII)-hypertension results in neuroinflammation and oxidative stress that will impair cognition in a MR-dependent manner.Methods: 16-17 week old male C57bl/6 mice were treated with AngII (800ng/kg/min) ± the MR antagonist, eplerenone (EPL;100mg/kg/day) for 4 weeks; Sham mice served as control. Data are presented as mean ± SEM; n=4-12 per group *=different from Sham.Results: AngII reduced astrocyte density and increased microglial density; the changes in microglia were prevented by EPL. AngII reduced the mRNA expression of brain-derived neurotrophic factor (BDNF), doublecortin, glial fibrillary acidic protein (GFAP), and synaptophysin (SYP); the reductions in BDNF, GFAP and SYP mRNA expression were prevented by EPL. We assessed cognitive function using the Barnes maze; AngII treated mice spent less time in the target quadrant than the sham or AngII+EPL mice. There was a trend toward there being an increase in the latency to reach the target quadrant in the AngII mice but the changes were not significant. Changes in nest building are associated with cognitive decline, nest building was impaired in AngII mice and these changes were prevented by EPL. There was a trend for oxidized proteins to be increased in AngII mice that may be prevented by EPL but these changes were not significant. Preliminary studies suggest that AngII changes the morphology of cortical neurons suggesting that the increased blood pressure may lead to unhealthy neurons.Conclusion: AngII-hypertension results in neuroinflammation and creates an environment where markers for neuronal support and synapse formation are impaired. These changes are regulated by MR signaling and may be associated with the declined cognitive function.

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