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杠柳叶提取物能减轻汞诱导的大鼠齿状回细胞增殖、神经母细胞分化及空间记忆损伤。

Leaf extracts from Dendropanax morbifera Léveille mitigate mercury-induced reduction of spatial memory, as well as cell proliferation, and neuroblast differentiation in rat dentate gyrus.

机构信息

Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 08826, South Korea.

Department of Anatomy, College of Medicine, Soonchunhyang University, Cheonan, Chungcheongnam, 31151, South Korea.

出版信息

BMC Complement Altern Med. 2019 May 2;19(1):94. doi: 10.1186/s12906-019-2508-6.

Abstract

BACKGROUND

The brain is susceptible to methylmercury toxicity, which causes irreversible damage to neurons and glia and the leaf extract Dendropanax morbifera Léveille (DML) has various biological functions in the nervous system. In this study, we examined the effects of DML on mercury-induced proliferating cells and differentiated neuroblasts.

METHODS

Dimethylmercury (5 μg/kg) and galantamine (5 mg/kg) was administered intraperitoneally and/or DML (100 mg/kg) was orally to 7-week-old rats every day for 36 days. One hour after the treatment, novel object recognition test was examined. In addition, spatial probe tests were conducted on the 6th day after 5 days of continuous training in the Morris swim maze. Thereafter, the rats were euthanized for immunohistochemical staining analysis with Ki67 and doublecortin and measurement for acetylcholinesterase (AChE) activity.

RESULTS

Dimethylmercury-treated rats showed reduced discrimination index in novel object recognition test and took longer to find the platform than did control group. Compared with dimethylmercury treatment alone, supplementation with DML or galatamine significantly ameliorated the reduction of discrimination index and reduced the time spent to find the platform. In addition, the number of platform crossings was lower in the dimethylmercury-treated group than in controls, while the administration of DML or galantamine significantly increased the number of crossings than did dimethylmercury treatment alone. Proliferating cells and differentiated neuroblasts, assessed by Ki67 and doublecortin immunohistochemical staining was significantly decreased in the dimethylmercury treated group versus controls. Supplementation with DML or galantamine significantly increased the number of proliferating cells and differentiated neuroblasts in the dentate gyrus. In addition, treatment with dimethylmercury significantly increased AChE activity in hippocampal homogenates, while treatment with dimethylmercury+DML or dimethylmercury+galantamine significantly ameliorated this increase.

CONCLUSIONS

These results suggest that DML may be a functional food that improves dimethylmercury-induced memory impairment and ameliorates dimethylmercury-induced reduction in proliferating cells and differentiated neuroblasts, and demonstrates corresponding activation of AChE activity in the dentate gyrus.

摘要

背景

大脑容易受到甲基汞毒性的影响,这会导致神经元和神经胶质不可逆的损伤,而五加科树参属植物(Dendropanax morbifera Léveille,DML)在神经系统中具有多种生物学功能。在这项研究中,我们研究了 DML 对汞诱导的增殖细胞和分化神经母细胞的影响。

方法

将二甲基汞(5μg/kg)和加兰他敏(5mg/kg)经腹腔内注射,或 DML(100mg/kg)每天口服给予 7 周龄大鼠,连续 36 天。治疗后 1 小时,进行新物体识别测试。此外,在 Morris 水迷宫连续训练 5 天后的第 6 天,进行空间探针测试。此后,通过 Ki67 和双皮质蛋白的免疫组织化学染色分析和乙酰胆碱酯酶(AChE)活性的测量,处死大鼠。

结果

二甲基汞处理的大鼠在新物体识别测试中的辨别指数降低,找到平台的时间长于对照组。与单独二甲基汞处理相比,DML 或加兰他敏的补充显著改善了辨别指数的降低,并减少了找到平台的时间。此外,与对照组相比,二甲基汞处理组的平台穿越次数较低,而 DML 或加兰他敏的给药显著增加了穿越次数,高于单独二甲基汞处理。Ki67 和双皮质蛋白免疫组织化学染色评估的增殖细胞和分化神经母细胞数量在二甲基汞处理组明显低于对照组。DML 或加兰他敏的补充显著增加了齿状回中的增殖细胞和分化神经母细胞数量。此外,二甲基汞处理显著增加了海马匀浆中的 AChE 活性,而二甲基汞+DML 或二甲基汞+加兰他敏的处理显著改善了这种增加。

结论

这些结果表明,DML 可能是一种功能性食品,可改善二甲基汞引起的记忆障碍,并改善二甲基汞引起的增殖细胞和分化神经母细胞减少,同时在齿状回中相应地激活 AChE 活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31bc/6498467/b0d102e410e5/12906_2019_2508_Fig1_HTML.jpg

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