Vitamin C reduces spatial learning deficits in middle-aged and very old APP/PSEN1 transgenic and wild-type mice
Vitamin C reduces spatial learning deficits in middle-aged and very old APP/PSEN1 transgenic and wild-type mice
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DOI：
10.1016/j.pbb.2009.06.006
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发表时间：
2009-10-01
影响因子：
3.6
通讯作者：
May, J. M.
中科院分区：
文献类型：
--
作者：
Harrison, F. E.;Hosseini, A. H.;May, J. M.
阿尔茨海默病是一种进行性和致命的神经退行性疾病，其特征是β淀粉样蛋白（A β）沉积物的积累、氧化应激升高和胆碱能系统的恶化。本研究调查了急性腹腔内（i. p.）APP/PSEN 1小鼠中的维生素C（抗坏血酸盐）治疗，APP/PSEN 1小鼠是阿尔茨海默病的小鼠模型。中年（12个月）和非常老（24个月）APP/PSEN 1双基因和野生型小鼠用抗坏血酸（125 mg/kg i. p.）或在Y-迷宫自发交替和Morris水迷宫任务测试前1小时给予载体。非常老的老鼠在认知任务上比中年老鼠表现得更差。抗坏血酸治疗改善了野生型和APP/PSEN 1小鼠在水迷宫中的Y-迷宫交替率和游泳准确性。A β沉积和氧化应激都随着年龄的增长而增加，与野生型小鼠相比，APP/PSEN 1中的乙酰胆碱酯酶（AChE）活性显着降低。然而，短期的急性抗坏血酸治疗并没有改变阿尔茨海默氏症样的神经病理学特征的斑块沉积，氧化应激，或乙酰胆碱酯酶活性。这些数据表明，抗坏血酸可能具有促智功能时，以高剂量胃肠外给药，其作用模式是通过急性，药理学样机制，可能调节神经递质功能。(C)2009 Elsevier Inc. All rights reserved.
Alzheimer's disease is a progressive and fatal neurodegenerative disease characterized by a build up of amyloid beta (A beta) deposits, elevated oxidative stress, and deterioration of the cholinergic system. The present study investigated short-term cognitive-enhancing effects of acute intraperitoneal (i.p.) Vitamin C (ascorbate) treatment in APP/PSEN1 mice, a mouse model of Alzheimer's disease. Middle-aged (12 months) and very old (24 months) APP/PSEN1 bigenic and wild-type mice were treated with ascorbate (125 mg/kg i.p.) or the vehicle 1 h before testing on Y-maze spontaneous alternation and Morris water maze tasks. Very old mice performed more poorly on cognitive tasks than middle-aged mice. Ascorbate treatment improved Y-maze alternation rates and swim accuracy in the water maze in both wild-type and APP/PSEN1 mice. A beta deposits and oxidative stress both increased with age, and acetylcholinesterase (AChE) activity was significantly reduced in APP/PSEN1 compared to wild-type mice. However, the short course of acute ascorbate treatment did not alter Alzheimer-like neuropathological features of plaque deposition, oxidative stress, or AChE activity. These data suggest that ascorbate may have nootropic functions when administered parenterally in high doses and that the mode of action is via an acute, pharmacological-like mechanism that likely modulates neurotransmitter function. (C) 2009 Elsevier Inc. All rights reserved.