Abstract
Recent studies have indicated that several anti-hypertensive drugs may delay the development and progression of Alzheimer’s disease (AD). However, the relationships among AD, hypertension, and oxidative stress remain to be elucidated. Here, we aimed to determine whether reactive oxygen species (ROS) reduction by resveratrol in the brain leads to cognitive impairment reduction in rats with angiotensin II (Ang-II)-induced early AD. Male Wistar Kyoto (WKY) rats with Ang-II-induced AD were treated with losartan or resveratrol for two weeks. Our results show decreased blood pressure, increased hippocampal brain-derived neurotrophic factor (BDNF) level, and decreased nucleus tractus solitarius (NTS) ROS production in the Ang-II groups with losartan (10 mg/kg), or resveratrol (10 mg/kg/day) treatment. Furthermore, losartan inhibition of hippocampal TauT231 phosphorylation activated AktS473 phosphorylation, and significantly abolished Ang-II-induced Aβ precursors, active caspase 3, and glycogen synthase kinase 3β (GSK-3β)Y216 expressions. Consistently, resveratrol showed similar effects compared to losartan. Both losartan and resveratrol restored hippocampal-dependent contextual memory by NADPH oxidase 2 (NOX2) deletion and superoxide dismutase 2 (SOD2) elevation. Our results suggest that both losartan and resveratrol exert neuroprotective effects against memory impairment and hippocampal damage by oxidative stress reduction in early stage AD rat model. These novel findings indicate that resveratrol may represent a pharmacological option similar to losartan for patients with hypertension at risk of AD during old age.
Highlights
Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder associated with abnormal energy metabolism, representing the most common neurodegenerative disorder worldwide [1,2]
A previous population-based study has revealed that hippocampal atrophy (HA) is usually attributed to the neurofibrillary tangles and neuritic plaques associated with AD [30]
Several studies have indicated that the clinical end points of AD are strongest in those who have never been treated for hypertension
Summary
Alzheimer’s disease (AD) is an age-dependent neurodegenerative disorder associated with abnormal energy metabolism, representing the most common neurodegenerative disorder worldwide [1,2]. Alzheimer’s disease is characterised neuropathologically by the formation of senile plaques and neurofibrillary tangles, and clinically by the progressive deterioration of memory and other cognitive functions [3] which cannot be prevented using any available treatments [4]. Kehoe [10] explained that, Angiotensin-converting enzyme (ACE) is normally abundant in neuronal density, ACE activity was higher in typical AD patients despite significant neuronal loss. They found that the elevated ACE activity correlated positively with the severity of tau pathology [11]
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