Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease †
1
Section of Neurology, Kaohsiung Veterans General Hospital, Kaohsiung 81300, Taiwan
2
Center for Geriatrics and Gerontology, Kaohsiung Veterans General Hospital, Kaohsiung 81300, Taiwan
3
Section of Neurology, Zouying Branch of Kaohsiung Armed Forces General Hospital Kaohsiung, Kaohsiung 81300, Taiwan
4
Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 81700, Taiwan
5
Department of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80400, Taiwan
6
Research Assistant Center, Show Chwan Memorial Hospital, Changhua 50000, Taiwan
7
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81300, Taiwan
8
Department of Internal Medicine, Division of Cardiology, Kaohsiung Veterans General Hospital, Kaohsiung 81300, Taiwan
9
Department of Pharmacology, Medical Research, China Medical University Hospital, China Medical University, Taichung 40400, Taiwan
10
Yuh-Ing Junior College of Health Care & Management, Kaohsiung 82100, Taiwan
11
Shu-Zen Junior College of Medicine and Management, Kaohsiung 80700, Taiwan
*
Authors to whom correspondence should be addressed.
†
This paper is an extended version of our conference paper in Proceedings of the 18th World Congress of Basic and Clinical Pharmacology (WCP2018), poster No. PO1-2-78.
‡
These authors contributed equally to this work.
J. Clin. Med. 2018, 7(10), 329; https://doi.org/10.3390/jcm7100329
Received: 21 August 2018 / Revised: 28 September 2018 / Accepted: 2 October 2018 / Published: 5 October 2018
(This article belongs to the Special Issue Mild Cognitive Impairment)
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.
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Keywords:
Alzheimer’s disease; central nervous system; hypertension; brain-derived neurotrophy factor; NADPH oxidase
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MDPI and ACS Style
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.
AMA Style
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 †. Journal of Clinical Medicine. 2018; 7(10):329.
Chicago/Turabian StyleLin, Yu-Te; Wu, Yi-Chung; Sun, Gwo-Ching; Ho, Chiu-Yi; Wong, Tzyy-Yue; Lin, Ching-Huang; Chen, Hsin-Hung; Yeh, Tung-Chen; Li, Chia-Jung; Tseng, Ching-Jiunn; Cheng, Pei-Wen. 2018. "Effect of Resveratrol on Reactive Oxygen Species-Induced Cognitive Impairment in Rats with Angiotensin II-Induced Early Alzheimer’s Disease †" J. Clin. Med. 7, no. 10: 329.
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