Effects of resveratrol on apoptosis in a rat model of vascular dementia

Sun,Zhi‑Kun; Ma,Xing‑Rong; Jia,Yan‑Jie; Liu,Yan‑Ru; Zhang,Jie‑Wen; Zhang,Bo‑Ai

doi:10.3892/etm.2014.1542

Effects of resveratrol on apoptosis in a rat model of vascular dementia

Authors:
- Zhi‑Kun Sun
- Xing‑Rong Ma
- Yan‑Jie Jia
- Yan‑Ru Liu
- Jie‑Wen Zhang
- Bo‑Ai Zhang
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Affiliations: Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, Henan 450002, P.R. China, Department of Neurology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450002, P.R. China
Published online on: February 13, 2014 https://doi.org/10.3892/etm.2014.1542
Pages: 843-848

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Abstract

Resveratrol is a natural polyphenol widely present in plants, particularly in the skin of red grapes and in wine. It possesses a wide range of biological effects and exhibits neuroprotective effects in numerous diseases. However, data evaluating the effects of resveratrol in vascular dementia (VaD) are lacking. In the present study, the permanent, bilateral common carotid artery occlusion rat model was used to study the effects of resveratrol on VaD. The Morris water maze was used to test the spatial learning and memory performance of the rats. The expression levels of Bax, Bcl‑2, cleaved caspase‑3 and cleaved poly(ADP‑ribose) polymerase (PARP) in the hippocampus were measured. The results showed that resveratrol inhibited memory impairment in the VaD rat model, and attenuated the increases in the expression levels of Bax, cleaved caspase‑3 and cleaved PARP and the reductions in the expression levels of Bcl‑2 that were induced by VaD. These results provide a novel insight into the neuroprotective effects of resveratrol and its possible therapeutic role in VaD.

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1	Wyllie AH: Apoptosis (the 1992 Frank Rose Memorial Lecture). Br J Cancer. 67:205–208. 1993. View Article : Google Scholar : PubMed/NCBI
2	Favaloro B, Allocati N, Graziano V, et al: Role of apoptosis in disease. Aging (Albany NY). 4:330–349. 2012.
3	Jellinger KA: The enigma of vascular cognitive disorder and vascular dementia. Acta Neuropathol. 113:349–388. 2007. View Article : Google Scholar : PubMed/NCBI
4	Ni J, Ohta H, Matsumoto K and Watanabe H: Progressive cognitive impairment following chronic cerebral hypoperfusion induced by permanent occlusion of bilateral carotid arteries in rats. Brain Res. 653:231–236. 1994. View Article : Google Scholar : PubMed/NCBI
5	Kim SK, Cho KO and Kim SY: White matter damage and hippocampal neurodegeneration induced by permanent bilateral occlusion of common carotid artery in the rat: Comparison between Wistar and Sprague-Dawley strain. Korean J Physiol Pharmacol. 12:89–94. 2008. View Article : Google Scholar
6	Cechetti F, Worm PV, Pereira LO, et al: The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate. Braz J Med Biol Res. 43:1178–1183. 2010. View Article : Google Scholar : PubMed/NCBI
7	Gong X, Ma M, Fan X, et al: Down-regulation of IGF-1/IGF-1R in hippocampus of rats with vascular dementia. Neurosci Lett. 513:20–24. 2012. View Article : Google Scholar : PubMed/NCBI
8	Takaoka M: Resveratrol, a new phenolic compound from Veratrum grandiflorum. Nippon Kagaku Kaishi. 60:1090e1001939.
9	Shen M, Wu RX, Zhao L, et al: Resveratrol attenuates ischemia/reperfusion injury in neonatal cardiomyocytes and its underlying mechanism. PLoS One. 7:e512232012. View Article : Google Scholar : PubMed/NCBI
10	Ku CR, Lee HJ, Kim SK, et al: Resveratrol prevents streptozotocin-induced diabetes by inhibiting the apoptosis of pancreatic β-cell and the cleavage of poly (ADP-ribose) polymerase. Endocr J. 59:103–109. 2012.PubMed/NCBI
11	Robb EL, Page MM, Wiens BE and Stuart JA: Molecular mechanisms of oxidative stress resistance induced by resveratrol: Specific and progressive induction of MnSOD. Biochem Biophys Res Commun. 367:406–412. 2008. View Article : Google Scholar : PubMed/NCBI
12	Bo S, Ciccone G, Castiglione A, et al: Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Curr Med Chem. 20:1323–1331. 2013. View Article : Google Scholar : PubMed/NCBI
13	Athar M, Back JH, Kopelovich L, et al: Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch Biochem Biophys. 486:95–102. 2009. View Article : Google Scholar : PubMed/NCBI
14	Simão F, Matté A, Breier AC, et al: Resveratrol prevents global cerebral ischemia-induced decrease in lipid content. Neurol Res. 35:59–64. 2013.PubMed/NCBI
15	Li Z, Pang L, Fang F, et al: Resveratrol attenuates brain damage in a rat model of focal cerebral ischemia via up-regulation of hippocampal Bcl-2. Brain Res. 1450:116–124. 2012. View Article : Google Scholar : PubMed/NCBI
16	Wu Z, Xu Q, Zhang L, et al: Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats. Neurochem Res. 34:1393–1400. 2009. View Article : Google Scholar : PubMed/NCBI
17	Pasinetti GM, Wang J, Marambaud P, et al: Neuroprotective and metabolic effects of resveratrol: therapeutic implications for Huntington’s disease and other neurodegenerative disorders. Exp Neurol. 232:1–6. 2011.PubMed/NCBI
18	Khan MM, Ahmad A, Ishrat T, et al: Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson’s disease. Brain Res. 1328:139–151. 2010.PubMed/NCBI
19	Li F, Gong Q, Dong H and Shi J: Resveratrol, a neuroprotective supplement for Alzheimer’s disease. Curr Pharm Des. 18:27–33. 2012.
20	Guidance suggestions for the care and use of laboratory animals. The Ministry of Science and Technology of the People’s Republic of China; Beijing: 2006
21	Ma XR, Sun ZK, Liu YR, et al: Resveratrol improves cognition and reduces oxidative stress in rats with vascular dementia. Neural Regen Res. 8:2050–2059. 2013.PubMed/NCBI
22	Sun ZK, Yang HQ, Pan J, et al: Protective effects of erythropoietin on tau phosphorylation induced by beta-amyloid. J Neurosci Res. 86:3018–3027. 2008. View Article : Google Scholar : PubMed/NCBI
23	Levine DA and Langa KM: Vascular cognitive impairment: disease mechanisms and therapeutic implications. Neurotherapeutics. 8:361–373. 2011. View Article : Google Scholar : PubMed/NCBI
24	Bennett S, Grant MM and Aldred S: Oxidative stress in vascular dementia and Alzheimer’s disease: a common pathology. J Alzheimers Dis. 17:245–257. 2009.
25	Wang J, Zhang HY and Tang XC: Cholinergic deficiency involved in vascular dementia: possible mechanism and strategy of treatment. Acta Pharmacol Sin. 30:879–888. 2009. View Article : Google Scholar : PubMed/NCBI
26	Gustafsson AB and Gottlieb RA: Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol. 292:C45–C51. 2007. View Article : Google Scholar : PubMed/NCBI
27	Wolter KG, Hsu YT, Smith CL, et al: Movement of Bax from the cytosol to mitochondria during apoptosis. J Cell Biol. 139:1281–1292. 1997. View Article : Google Scholar : PubMed/NCBI
28	Clementi ME, Pezzotti M, Orsini F, et al: Alzheimer’s amyloid beta-peptide (1-42) induces cell death in human neuroblastoma via bax/bcl-2 ratio increase: an intriguing role for methionine 35. Biochem Biophys Res Commun. 342:206–213. 2006.
29	Sun ZK, Yang HQ, Wang ZQ, et al: Erythropoietin prevents PC12 cells from beta-amyloid-induced apoptosis via PI3K/Akt pathway. Transl Neurodegener. 1:72012. View Article : Google Scholar : PubMed/NCBI
30	Grütter MG: Caspases: key players in programmed cell death. Curr Opin Struct Biol. 10:649–655. 2000.
31	Lee MK, Kang SJ, Poncz M, et al: Resveratrol protects SH-SY5Y neuroblastoma cells from apoptosis induced by dopamine. Exp Mol Med. 39:376–384. 2007. View Article : Google Scholar : PubMed/NCBI
32	Alvarez-Gonzalez R, Spring H, Müller M and Bürkle A: Selective loss of poly(ADP-ribose) and the 85-kDa fragment of poly(ADP-ribose) polymerase in nucleoli during alkylation-induced apoptosis of HeLa cells. J Biol Chem. 274:32122–32126. 1999. View Article : Google Scholar : PubMed/NCBI
33	Lee DH, Park T and Kim HW: Induction of apoptosis by disturbing mitochondrial-membrane potential and cleaving PARP in Jurkat T cells through treatment with acetoxyscirpenol mycotoxins. Biol Pharm Bull. 29:648–654. 2006. View Article : Google Scholar
34	Oliver FJ, de la Rubia G, Rolli V, et al: Importance of poly(ADP-ribose) polymerase and its cleavage in apoptosis. Lesson from an uncleavable mutant. J Biol Chem. 273:33533–33539. 1998. View Article : Google Scholar : PubMed/NCBI