Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice

Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice
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淫羊藿苷对衰老加速小鼠 pron 8 (SAMP8) 小鼠记忆障碍和神经化学缺陷的神经保护作用

DOI:
10.1016/j.brainres.2010.03.084
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发表时间:
2010-06-02
期刊:
影响因子:
2.9
通讯作者:
Du, Guan-Hua
Du, Guan-Hua
中科院分区:
医学3区
文献类型:
--
作者:
He, Xiao-Li;Zhou, Wei-Qin;Du, Guan-Hua

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衰老加速型小鼠8型(SAMP 8)是一种新的衰老模型,其特征在于衰老的早期发生和快速进展。在本研究中,对6个月大的雄性SAMP 8小鼠口服淫羊藿苷(75,150 mg/kg)15周。采用通道水迷宫实验和跳台被动回避实验评价小鼠认知功能障碍。采用高效液相色谱-电化学法测定脑内单胺含量。观察淫羊藿苷对SAMP 8小鼠氧化应激和乙酰胆碱酯酶(AChE)活性的影响。结果表明,淫羊藿苷对SAMP 8小鼠的通道水迷宫和跳台实验中的学习记忆障碍有明显的保护作用。淫羊藿苷可部分逆转SAMP 8小鼠大脑皮层和海马单胺类及代谢物水平的改变。此外,淫羊藿苷还能显著降低SAMP 8小鼠脑组织和血清中丙二醛(MDA)和一氧化氮(NO)含量,降低一氧化氮合酶(NOS)活性,提高谷胱甘肽过氧化物酶(GSH-Px)和超氧化物歧化酶(SOD)活性。同时,淫羊藿苷对乙酰胆碱酯酶活性有明显的抑制作用。然而,阳性对照吡拉西坦未显示出显著的有益效果。总之,本研究结果表明,淫羊藿苷对SAMP 8小鼠认知障碍的改善可能是由于增加单胺水平,抑制氧化损伤和降低乙酰胆碱酯酶活性。(c)2010 Elsevier B. V.保留所有权利。
The senescence-accelerated mouse prone 8 (SAMP8) is a novel aging model characterized by early onset and rapid advancement of senescence. In the present study, 6-month-old male SAMP8 mice were orally administered icariin (75,150 mg/kg) for 15 weeks. Mice were submitted to passageway water maze test and step-down passive avoidance test for evaluating cognitive impairments. The HPLC-EC technique was used to determine the monoamine contents in the brain. The effects of icariin on oxidative stress and the acetylcholinesterase (AChE) activity of SAMP8 mice were also investigated. We found that icariin treatment significantly prevented learning and memory impairments of SAMP8 mice in passageway water maze test and step-down test. Icariin could partly reverse alterations of monoamines and metabolites levels in the cortex and hippocampus of SAMP8 mice. Furthermore, icariin-treated SAMP8 mice had significantly decreased malondialdehyde (MDA), nitric oxide (NO) contents, lowered nitric oxide synthase (NOS) activity and higher glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in the brain homogenates and serum. Meanwhile, the acetylcholinesterase activity was markedly inhibited after icariin administration. However, the positive control piracetam did not show significant beneficial effects. In conclusion, the present findings demonstrated that the improvement of icariin on cognitive impairments in SAMP8 mice may be due to increasing monoamines levels, inhibiting oxidative damage and decreasing acetylcholinesterase activity. (c) 2010 Elsevier B.V. All rights reserved.