Preprint Article Version 1 This version is not peer-reviewed

Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease

Version 1 : Received: 21 August 2018 / Approved: 21 August 2018 / Online: 21 August 2018 (06:04:03 CEST)

A peer-reviewed article of this Preprint also exists.

Lin, Y.-T.; Wu, Y.-C.; Sun, G.-C.; Ho, C.-Y.; Wong, T.-Y.; Lin, C.-H.; Chen, H.-H.; Yeh, T.-C.; Li, C.-J.; Tseng, C.-J.; Cheng, P.-W. Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease . J. Clin. Med. 2018, 7, 329. Lin, Y.-T.; Wu, Y.-C.; Sun, G.-C.; Ho, C.-Y.; Wong, T.-Y.; Lin, C.-H.; Chen, H.-H.; Yeh, T.-C.; Li, C.-J.; Tseng, C.-J.; Cheng, P.-W. Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease †. J. Clin. Med. 2018, 7, 329.

Journal reference: J. Clin. Med. 2018, 7, 329
DOI: 10.3390/jcm7100329

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. In the present study, we aimed to determine whether treatment with resveratrol reduces reactive oxygen species (ROS) generation in the brain, thereby reducing cognitive impairment in rats with angiotensin II (Ang-II)-induced early AD. Male WKY rats with Ang-II-induced AD were treated with losartan or resveratrol for 2 weeks. Our results revealed that treatment with resveratrol (10 mg/kg/day) decreased blood pressure, increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus, and decreased ROS production in the nucleus tractus solitarius (NTS) in the Ang-II groups. In addition, inhibition of TauT231 phosphorylation in the hippocampus using resveratrol significantly abolished Ang-II-induced expression of Ab precursors, active caspase 3, and glycogen synthase kinase 3b (GSK-3b)Y216 while increasing AktS473 phosphorylation. Notably, resveratrol reversed impairments in hippocampal-dependent contextual memory induced by deleting NADPH oxidase and NOX2. Overall, our results suggest that resveratrol exerts neuroprotective effects against memory impairment and hippocampal damage in a rat model of early stage AD by reducing oxidative stress. These novel findings indicate that resveratrol may represent a pharmacological option for patients with hypertension at a risk of AD during old age.

Subject Areas

Alzheimer’s disease; central nervous system; hypertension; brain-derived neurotrophy factor; NADPH oxidase

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