Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.
Centella asiatica attenuates Aβ-induced neurodegenerative spine loss and dendritic simplification.
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DOI：
10.1016/j.neulet.2017.02.072
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发表时间：
2017-04-12
影响因子：
2.5
通讯作者：
Soumyanath A
中科院分区：
文献类型：
--
作者：
Gray NE;Zweig JA;Murchison C;Caruso M;Matthews DG;Kawamoto C;Harris CJ;Quinn JF;Soumyanath A
药用植物Centella asiatica长期以来一直用于改善记忆和认知功能。我们之前已经证明，植物水提取物（CAW）对阿尔茨海默病小鼠模型中淀粉样蛋白-β（Aβ）暴露的有害认知影响具有神经保护作用，并改善健康老年小鼠的学习和记忆。这项研究通过检查CAW以及提取物中发现的化合物如何调节Aβ暴露神经元的突触健康来探索这些效应的生理基础。使用来自淀粉样前体蛋白过表达Tg 2576小鼠及其野生型（WT）同窝仔的海马神经元，研究CAW和提取物中发现的各种化合物对Aβ诱导的树突简化和突触丢失的影响。CAW增强WT神经元的树枝状和棘密度，并防止Aβ暴露引起的Tg 2576神经元树突生长减少和棘丢失。三萜类化合物存在于CAW被发现类似地改善树枝化，虽然他们没有影响棘密度。相反，来自CAW的咖啡酰奎尼酸（CQA）化合物能够调节这两个终点，尽管哪种CQA介导哪种效应存在特异性。这些数据表明，CAW和其中发现的几种化合物可以在Aβ暴露的情况下改善树突分支和突触分化，这可能是体内响应提取物观察到的认知改善的基础。此外，由于CAW及其组成化合物也改善了WT神经元中的这些终点，因此这些结果可能指向提取物在阿尔茨海默病之外的更广泛的治疗用途。
The medicinal plant Centella asiatica has long been used to improve memory and cognitive function. We have previously shown that a water extract from the plant (CAW) is neuroprotective against the deleterious cognitive effects of amyloid-β (Aβ) exposure in a mouse model of Alzheimer’s disease, and improves learning and memory in healthy aged mice as well. This study explores the physiological underpinnings of those effects by examining how CAW, as well as chemical compounds found within the extract, modulate synaptic health in Aβ-exposed neurons. Hippocampal neurons from amyloid precursor protein over-expressing Tg2576 mice and their wild-type (WT) littermates were used to investigate the effect of CAW and various compounds found within the extract on Aβ-induced dendritic simplification and synaptic loss. CAW enhanced arborization and spine densities in WT neurons and prevented the diminished outgrowth of dendrites and loss of spines caused by Aβ exposure in Tg2576 neurons. Triterpene compounds present in CAW were found to similarly improve arborization although they did not affect spine density. In contrast caffeoylquinic acid (CQA) compounds from CAW were able to modulate both of these endpoints, although there was specificity as to which CQAs mediated which effect. These data suggest that CAW, and several of the compounds found therein, can improve dendritic arborization and synaptic differentiation in the context of Aβ exposure which may underlie the cognitive improvement observed in response to the extract in vivo. Additionally, since CAW, and its constituent compounds, also improved these endpoints in WT neurons, these results may point to a broader therapeutic utility of the extract beyond Alzheimer’s disease.
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影响因子：
5.4
作者：
Gray NE;Harris CJ;Quinn JF;Soumyanath A
通讯作者：
Soumyanath A
表达人类野生型Tau的转基因小鼠的树突复杂性和脊柱形态的变化。
影响因子：
3.1
作者：
Dickstein, Dara L.;Brautigam, Hannah;Stockton, Steven D., Jr.;Schmeidler, James;Hof, Patrick R.
通讯作者：
Hof, Patrick R.
影响因子：
5.3
作者：
Snigdha, Shikha;Prieto, G. Aleph;Cotman, Carl W.
通讯作者：
Cotman, Carl W.
影响因子：
14.8
作者：
Kaech, Stefanie;Banker, Gary
通讯作者：
Banker, Gary
DOI：
10.1007/bf03190180
发表时间：
1993-10-01
影响因子：
1.9
作者：
RUSH, WR;MURRAY, GR;GRAHAM, DJM
通讯作者：
GRAHAM, DJM