Quercetin reverses D-galactose induced neurotoxicity in mouse brain

Quercetin reverses D-galactose induced neurotoxicity in mouse brain
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DOI:
10.1016/j.bbr.2006.03.043
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发表时间:
2006-08-10
影响因子:
2.7
通讯作者:
Feng, You-jian
Feng, You-jian
中科院分区:
心理学3区
文献类型:
--
作者:
Lu, Jun;Zheng, Yuan-lin;Feng, You-jian

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采用行为学方法研究了槲皮素5和10 mg/(kg·d)对D-半乳糖(50 mg/(kg·d))腹腔注射昆明种小鼠的神经保护作用。与D-半乳糖处理组相比,槲皮素处理组小鼠在新环境刺激诱导下表现出更高的活动性,在旷场任务中表现出更低的焦虑和更高的新奇寻求行为,在避暗和Morris水迷宫测试中表现出更好的学习和记忆能力。我们进一步研究了槲皮素对小鼠脑神经保护作用的机制。槲皮素显著提高超氧化物歧化酶(SOD)活性,降低丙二醛(MDA)水平。这些结果表明,槲皮素可以逆转D-半乳糖诱导的小鼠脑氧化损伤。神经毒性也与氧化应激诱导的Ca 2+超载有关。槲皮素能维持D-gal处理小鼠脑内Ca ~(2+)稳态。此外,我们还研究了生长相关蛋白GAP 43 mRNA的表达在小鼠脑组织中的原位杂交。我们发现槲皮素显著提高了D-gal处理小鼠脑中GAP 43 mRNA的表达,以恢复神经元的正常功能,对抗D-gal引起的细胞损伤。(c)2006 Elsevier B. V.保留所有权利。
We assessed the neuroprotective effects of quercetin-feeding at doses of 5 and 10mg/(kg day) on Kunming mice injected daily with D-gal (50 mg/(kg day)) by behavioral tests. Quercetin-fed mice showed higher activity upon induction by new environmental stimuli, lower anxiety and higher novelty-seeking behavior in the open field tasks, and significantly improved learning and memory ability in step-through and Morris water Maze tests compared with D-gal-treated mice. We further investigated the mechanisms involved in the neuroprotective effects of quercetin on mouse brain. Quercetin significantly increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) level. These results imply that quercetin can reverse oxidant impairment induced by D-gal in mouse brain. Neurotoxicity is also associated with Ca2+ overload induced by oxidant stress. Quercetin could maintain the Ca2+ homeostasis in the brain Of D-gal-treated mice. Furthermore, we also examined the expression of growth-associated protein GAP43 mRNA in mouse brain by in situ hybridization. We found that quercetin dramatically elevated the GAP43 mRNA expression in the brain Of D-gal-treated mice to regenerate normal function of neurons against the cellular injury caused by D-gal. (c) 2006 Elsevier B.V. All rights reserved.