Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat

Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat
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DOI:
10.1016/j.phrs.2009.12.008
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发表时间:
2010-03-01
影响因子:
9.3
通讯作者:
Shukla, Rakesh
Shukla, Rakesh
中科院分区:
医学1区
文献类型:
--
作者:
Agrawal, Rahul;Mishra, Bhanvi;Shukla, Rakesh

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姜黄素是姜黄的主要类姜黄素,在几种神经退行性疾病如阿尔茨海默型痴呆中表现出有益的作用。最近的证据表明,脑胰岛素受体(IR)参与痴呆症的病理生理。本研究旨在探讨姜黄素对侧脑室注射链脲佐菌素(STZ)所致痴呆大鼠记忆功能、脑内IR、乙酰胆碱酯酶(AChE)活性及氧化应激的影响。在第1天和第3天,大鼠双侧注射STZ(3mg/kg,ICV)两次,并在治疗前和治疗后时间表中施用姜黄素(200mg/kg,po)。STZ(ICV)治疗组表现出记忆障碍,如Morris水迷宫测试的潜伏期时间没有显著减少,海马和大脑皮质IR蛋白水平显著降低。STZ(ICV)治疗大鼠的姜黄素治疗前和治疗后显著恢复了这两个区域的记忆缺陷和IR蛋白水平。此外,STZ(ICV)导致海马和大脑皮层AChE活性增强,姜黄素治疗前后使其正常化。STZ处理组海马和大脑皮质MDA水平升高,GSH水平降低,提示氧化应激状态,姜黄素处理前后也能减轻氧化应激状态。提示姜黄素对STZ所致痴呆模型的保护作用除具有抗胆碱酯酶和抗氧化活性外,还可能与其对脑IR的影响有关。(C)2010爱思唯尔有限公司版权所有。
Curcumin, the principal curcuminoid of turmeric, exhibits beneficial role in several neurodegenerative disorders such as dementia of Alzheimer type. Recent evidences suggest the involvement of brain insulin receptors (IRs) in the pathophysiology of dementia disorders. Therefore, the present study was undertaken to investigate the effect of curcumin on memory functions, brain IRs, acetylcholinesterase (AChE) activity and oxidative stress in intracerebroventricular (ICV) administered streptozotocin (STZ) induced dementia in rats. Rats were injected with STZ (3 mg/kg, ICV) bilaterally twice, on day 1 and 3 and curcumin (200 mg/kg, po) was administered in pre- and post-treatment schedules. STZ (ICV) treated group had shown memory deficit as indicated by no significant decrease in latency time in Morris water maze test and significant decrease in IR protein level in both hippocampus and cerebral cortex. Pre- and post-treatment of curcumin in STZ (ICV) treated rats significantly restored the memory deficit and IR protein level in both the regions. Furthermore, STZ (ICV) resulted into enhanced AChE activity in hippocampus and cerebral cortex which was normalized by curcumin pre- and post-treatment. An increase in MDA level and decrease in GSH level were obtained in both hippocampus and cerebral cortex in STZ treated group, indicating state of oxidative stress, which was also attenuated by pre- and post-treatment of curcumin. The results suggest that besides the anticholinesterase and antioxidant activity, effect on brain IR may also be an important factor for protective effect of curcumin against STZ induced dementia model. (C) 2010 Elsevier Ltd. All rights reserved.