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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >The ketogenic diet changes metabolite levels in hippocampal extracellular fluid.
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The ketogenic diet changes metabolite levels in hippocampal extracellular fluid.

机译：生酮饮食会改变海马细胞外液中的代谢产物水平。

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Despite successful use of the ketogenic diet (KD) for the treatment of drug-resistant epilepsy, its mechanism of action is unclear. After KD-feeding, increased plasma D-beta-hydroxybutyrate (BHB) levels appear to be important for protection against seizures. We hypothesized that the KD leads to metabolic changes in the brain, which are reflected in the hippocampal extracellular fluid (hECF). CD1 mice were fed control or KD for 2-3 weeks since weaning. In vivo microdialysis of hECF was used to measure the levels of glucose, lactate, as well as BHB under basal conditions and during 30 min stimulation with 60 mM K(+), which was retrodialysed. The hECF BHB concentration in KD-fed mice was determined as 43.4+/-10.1 muM using the zero-flow method and 50.7+/-5.5 muM based on in vitro recovery. The total BHB concentration in brain homogenate from KD-fed mice was 180 nmol/g. The intracellular BHB concentration is therefore estimated to be about 3-fold higher than the extracellular level, which suggests that BHB in adolescent mouse brains may not be quickly metabolized. The basal hECF glucose concentration was 30% lower in KD-fed mice, indicating that glucose may be less important as an energy source. Lactate levels were similar in control and KD-fed mice. High potassium stimulation elevated lactate by 3-3.5-fold and decreased glucose by 40-50% in both diet groups, consistent with similar anaerobic and aerobic metabolism in both diet groups during high hippocampal activity. Overall, these data (1) defined the BHB concentration in the hippocampal extracellular fluid in KD-fed mice and (2) showed lower glucose metabolism compared to control diet-fed mice. This work will now enable other researchers to mimic the hippocampal extracellular environment in experiments aimed at deciphering the mechanisms of the KD.
机译：尽管成功地使用了生酮饮食（KD）来治疗耐药性癫痫，但其作用机理尚不清楚。喂食KD后，血浆D-β-羟基丁酸酯（BHB）水平升高似乎对预防癫痫发作很重要。我们假设KD导致大脑的代谢变化，这反映在海马细胞外液（hECF）中。自断奶以来，对CD1小鼠喂食对照或KD 2-3周。 hECF的体内微透析用于测量碱性条件下以及经60 mM K（+）刺激30分钟后的葡萄糖，乳酸和BHB的水平，并进行透析。使用零流量法将KD喂养小鼠中的hECF BHB浓度确定为43.4 +/- 10.1μM，根据体外恢复，将其确定为50.7 +/- 5.5μM。来自KD喂养小鼠的脑匀浆中的总BHB浓度为180 nmol / g。因此，估计细胞内BHB的浓度比细胞外水平高约3倍，这表明青春期小鼠大脑中的BHB可能不会迅速代谢。在KD喂养的小鼠中，基础hECF葡萄糖浓度降低了30％，表明葡萄糖作为能量来源可能不那么重要。对照和KD喂养的小鼠中的乳酸水平相似。在两个饮食组中，高钾刺激使乳酸增加3-3.5倍，使葡萄糖减少40-50％，这与在高海马活动期间两个饮食组中相似的无氧和有氧代谢有关。总体而言，这些数据（1）定义了KD喂养小鼠的海马细胞外液中BHB的浓度，（2）与对照组饮食喂养的小鼠相比，葡萄糖代谢较低。这项工作现在将使其他研究人员能够在旨在破解KD机制的实验中模仿海马细胞外环境。

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