A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia
A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia
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DOI：
10.1016/j.neuropharm.2009.01.005
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发表时间：
2009-03-01
影响因子：
4.7
通讯作者：
Nath, Chandishwar
中科院分区：
文献类型：
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作者：
Agrawal, Rahul;Tyagi, Ethika;Nath, Chandishwar
本研究在脑室内（ICV）链脲佐菌素（STZ）诱导的痴呆模型中，研究了脑胰岛素受体（IR）在记忆功能中的作用及其与不同脑区乙酰胆碱酯酶（AChE）活性和氧化应激的相关性。在第1天和第3天用STZ（3 mg/kg，ICV）处理大鼠。多奈哌齐（5 mg/kg po）和褪黑激素（20 mg/kg ip）按治疗前和治疗后时间表给药。在第14天进行Morris水迷宫试验，并在第1次注射STZ后第21天处死动物。多奈哌齐和褪黑素对STZ组大鼠的潜伏期无明显拮抗作用，提示STZ组存在记忆障碍。与对照组相比，训练组大鼠海马IR蛋白水平显著升高，而STZ组大鼠海马IR蛋白水平显著降低，提示IR与记忆功能有关。STZ诱导的IR降低可被褪黑素逆转，但不能被多奈哌齐逆转。与对照相比，褪黑激素本身未显示IR水平的任何显著变化。M组海马AChE活性（DS和SS组分）较训练组增加，而多奈哌齐和褪黑素可抑制M组海马AChE活性。STZ组MDA水平升高，GSH水平降低，表明氧化应激，多奈哌齐和褪黑素可减轻氧化应激。抗氧化剂褪黑激素而不是抗胆碱酯酶剂多奈哌齐对STZ诱导的IR变化的有效性表明，IR受氧化应激的影响大于胆碱能变化。(C)2009爱思唯尔有限公司版权所有。
In the present study, role of brain insulin receptors (IRs) in memory functions and its correlation with acetylcholinesterase (AChE) activity and oxidative stress in different brain regions were investigated in intracerebroventricular (ICV) streptozotocin (STZ) induced dementia model. Rats were treated with STZ (3 mg/kg, ICV) on day 1 and 3. Donepezil (5 mg/kg po) and melatonin (20 mg/kg ip) were administered in pre- and post-treatment schedules. Morris water maze test was done on day 14 and animals were sacrificed on day 21 from 1st STZ injection. Memory deficit was found in STZ group as indicated by no significant decrease in latency time antagonized by donepezil and melatonin. IR protein level was found significantly increased in trained group as compared to control, whereas STZ decreased IR level significantly as compared to trained rats in hippocampus which indicates that IR is associated with memory functions. STZ induced decrease in IR was reversed by melatonin but not by donepezil. Melatonin per se did not show any significant change in IR level as compared to control. AChE activity (DS and SS fraction) was found to be increased in hippocampus in M group as compared to trained which was inhibited by donepezil and melatonin. Increase in MDA level and decrease in GSH level were obtained in STZ group indicating oxidative stress, which was attenuated by donepezil and melatonin. Effectiveness of antioxidant, melatonin but not of anti-cholinesterase, donepezil against STZ induced changes in IR indicates that IR is more affected with oxidative stress than cholinergic changes. (C) 2009 Elsevier Ltd. All rights reserved.