Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice.
Centella asiatica attenuates hippocampal mitochondrial dysfunction and improves memory and executive function in β-amyloid overexpressing mice.
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DOI：
10.1016/j.mcn.2018.09.002
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Soumyanath A
中科院分区：
文献类型：
--
作者：
Gray NE;Zweig JA;Caruso M;Zhu JY;Wright KM;Quinn JF;Soumyanath A
Centella asiatica是一种用于增强记忆力的药用植物。我们之前已经证明，积雪草（CAW）的水提取物可以减轻β-淀粉样蛋白（A β）诱导的小鼠空间记忆缺陷，并改善神经元健康。然而，CAW对其他认知领域的影响仍未被探索，其改善A β相关认知障碍的体内机制也是如此。本研究在A β蓄积的5 × FAD模型中研究了CAW对学习、记忆和执行功能以及线粒体功能和抗氧化反应的影响。在行为测试之前，将7个月大的5 × FAD雌性小鼠在其饮用水中用CAW（2mg/mL）处理两周。采用物体位置记忆任务（OLM）、条件性恐惧反应（CFR）和气味辨别反转学习（ODRL）测试评价学习、记忆和执行功能。使用Seahorse XF平台分析从这些动物分离的海马线粒体中的线粒体功能，并收获组织用于评估线粒体、抗氧化剂和突触蛋白。CAW改善了5 × FAD中所有行为测试的表现，但对WT动物没有影响。CAW处理的5 × FAD小鼠海马线粒体功能得到改善，海马和皮质线粒体基因表达增加。在WT和5 × FAD小鼠中，CAW处理也增加了转录因子NRF2及其抗氧化靶酶的基因表达。CAW治疗还减少了治疗的5 × FAD小鼠海马中的A β斑块负荷，但对皮质中的斑块没有影响。这些数据表明，CAW可以改善5 × FAD小鼠A β相关认知障碍的多个方面。口服CAW也可减轻这些动物的海马线粒体功能障碍。由于线粒体功能障碍和氧化应激伴随着阿尔茨海默病以外的许多病理条件下的认知障碍，这表明CAW的潜在广泛的治疗用途。
Centella asiatica is a medicinal plant used to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates β-amyloid (Aβ)-induced spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its In vivo mechanism of improving Aβ-related cognitive impairment. This study investigates the effects of CAW on learning, memory and executive function as well as mitochondrial function and antioxidant response in the 5×FAD model of Aβ accumulation. Seven month old 5×FAD female mice were treated with CAW (2mg/mL) in their drinking water for two weeks prior to behavioral testing. Learning, memory and executive function were assessed using the object location memory task (OLM), conditioned fear response (CFR) and odor discrimination reversal learning (ODRL) test. Mitochondrial function was profiled using the Seahorse XF platform in hippocampal mitochondria isolated from these animals and tissue was harvested for assessment of mitochondrial, antioxidant and synaptic proteins. CAW improved performance in all behavioral tests in the 5×FAD but had no effect on WT animals. Hippocampal mitochondrial function was improved and hippocampal and cortical expression of mitochondrial genes was increased in CAW-treated 5×FAD mice. Gene expression of the transcription factor NRF2, as well as its antioxidant target enzymes, was also increased with CAW treatment in both WT and 5×FAD mice. CAW treatment also decreased Aβ-plaque burden in the hippocampus of treated 5×FAD mice but had no effect on plaques in the cortex. These data show that CAW can improve many facets of Aβ-related cognitive impairment in 5×FAD mice. Oral treatment with CAW also attenuates hippocampal mitochondrial dysfunction in these animals. Because mitochondrial dysfunction and oxidative stress accompany cognitive impairment in many pathological conditions beyond Alzheimer’s disease, this suggests potentially broad therapeutic utility of CAW.
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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
影响因子：
2.5
作者：
Gray NE;Zweig JA;Murchison C;Caruso M;Matthews DG;Kawamoto C;Harris CJ;Quinn JF;Soumyanath A
通讯作者：
Soumyanath A
DOI：
10.1073/pnas.1006586107
发表时间：
2010-10-26
影响因子：
11.1
作者：
Du, Heng;Guo, Lan;Yan, Shirley ShiDu
通讯作者：
Yan, Shirley ShiDu
影响因子：
1.9
作者：
Good, Mark A.;Hale, Gemma
通讯作者：
Hale, Gemma
影响因子：
2.7
作者：
Assini, Fabricio Luiz;Duzzioni, Marcelo;Takahashi, Reinaldo Naoto
通讯作者：
Takahashi, Reinaldo Naoto