Introduction

Approximately 1% of the world’s population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD’s success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation.

Objectives

The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy.

Methods

FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5).

Results

Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1−/−. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane.

Conclusion

Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.

中文翻译：

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癫痫小鼠模型血脂变化

介绍

世界上大约 1% 的人口受到癫痫症的影响，癫痫症是一种以癫痫发作为特征的慢性神经系统疾病。三分之一的癫痫患者对 AED 具有耐药性，或者患有难治性癫痫 (MRE)。MRE 的一种非侵入性治疗方法包括生酮饮食，一种高脂肪、低碳水化合物的饮食。尽管生酮饮食在减轻癫痫发作方面取得了成功，但它也存在一些风险，而且其机制仍知之甚少。KD 已被证明可以改善癫痫表型的新陈代谢和线粒体功能。钾通道对癫痫病有影响，因为它们具有代谢传感器和控制神经元兴奋的双重作用。

目标

本研究的目的是探讨 Kv1.1-KO 癫痫模型海马和皮质组织脂质组的变化。

方法

利用 FT-ICR/MS 分析来检查从 Kv1.1 通道敲除癫痫小鼠模型 (n = 5) 和野生型小鼠 (n = 5) 中分离的皮质和海马组织的非极性代谢组。

结果

观察到不同的代谢特征，海马体的显着特征（p < 0.05）经常上调（FC ≥ 2），而皮质则下调（FC ≤ 0.5）。通路富集分析显示脂质生物合成受到影响。分配比分析表明，大多数代谢物的比例在Kv1.1−/− 中呈增加趋势。海马组织中的代谢物通常上调，表明海马体中发生了癫痫发作。线粒体功能异常与心磷脂（线粒体膜中的常见成分）的上调有关。

结论

一般来说，我们的研究发现海马和皮质中的脂质组响应 Kv1.1-KO 而发生变化，表明膜结构完整性和突触传递发生变化。