All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research.
All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research.
复制标题
您所需要的只是癫痫发作控制：使用变形虫来推进癫痫研究。
DOI：
10.3389/fncel.2018.00199
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发表时间：
2018
影响因子：
5.3
通讯作者：
Williams RSB
中科院分区：
文献类型：
--
作者：
Warren EC;Walker MC;Williams RSB
自从20世纪20年代通过饥饿控制癫痫发作的最初报告以来，生酮饮食一直被认为是一种能量相关的治疗方法。假设饮食通过减少碳水化合物摄入调节细胞能量状态的作用发挥作用，从而引起癫痫控制。根据这一假设，饥饿期间酮的产生为这种能量状态的改变提供了一种有吸引力的机制;然而，多年的研究一直在寻找癫痫发作控制和酮水平之间的联系，但在很大程度上失败了。由于这种对酮的关注，很少有研究检查游离脂肪酸在癫痫控制中的作用，游离脂肪酸是饮食中提供的甘油三酯和酮之间的代谢中间体。最近的发现表明，通过中链甘油三酯（MCT）生酮饮食提供的中链脂肪可能是癫痫控制饮食的关键治疗机制。在这里，我们描述了一个不寻常的途径，导致这一发现，开始使用一个易处理的非动物模型-Dictyosteoblasts，通过演示中链脂肪在癫痫控制中发挥直接作用，最后确定这些脂肪和相关同系物的作用机制，导致神经兴奋性降低和癫痫控制。
Since the original report of seizure control through starvation in the 1920s, the ketogenic diet has been considered an energy-related therapy. The diet was assumed to be functioning through the effect of reduced carbohydrate intake regulating cellular energy state, thus giving rise to seizure control. From this assumption, the generation of ketones during starvation provided an attractive mechanism for this altered energy state; however, many years of research has sought and largely failed to correlate seizure control and ketone levels. Due to this focus on ketones, few studies have examined a role for free fatty acids, as metabolic intermediates between the triglycerides provided in the diet and ketones, in seizure control. Recent discoveries have now suggested that the medium-chain fats, delivered through the medium-chain triglyceride (MCT) ketogenic diet, may provide a key therapeutic mechanism of the diet in seizure control. Here we describe an unusual pathway leading to this discovery, beginning with the use of a tractable non-animal model—Dictyostelium, through to the demonstration that medium-chain fats play a direct role in seizure control, and finally the identification of a mechanism of action of these fats and related congeners leading to reduced neural excitability and seizure control.
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DOI：
10.1124/jpet.114.218768
发表时间：
2015-01-01
影响因子：
3.5
作者：
Chang, Pishan;Zuckermann, Alexandra M. E.;Williams, Robin S. B.
通讯作者：
Williams, Robin S. B.
酮体通过线粒体渗透性过渡介导抗性作用。
影响因子：
11.2
作者：
Kim, Do Young;Simeone, Kristina A.;Simeone, Timothy A.;Pandya, Jignesh D.;Wilke, Julianne C.;Ahn, Younghee;Geddes, James W.;Sullivan, Patrick G.;Rho, Jong M.
通讯作者：
Rho, Jong M.
影响因子：
4.7
作者：
Lusardi TA;Akula KK;Coffman SQ;Ruskin DN;Masino SA;Boison D
通讯作者：
Boison D
影响因子：
4.7
作者：
Hughes, Sean David;Kanabus, Marta;Heales, Simon J. R.
通讯作者：
Heales, Simon J. R.
影响因子：
15.9
作者：
Lutas A;Yellen G
通讯作者：
Yellen G