Changes in lipid profiles of epileptic mouse model.
Changes in lipid profiles of epileptic mouse model.
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DOI：
10.1007/s11306-020-01729-4
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发表时间：
2020-10-06
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影响因子：
--
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中科院分区：
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世界上大约1%的人口受到癫痫的影响，癫痫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AEDs耐药，或患有难治性癫痫（MRE）。MRE的一种非侵入性治疗包括生酮饮食，一种高脂肪、低碳水化合物的饮食。尽管KD在癫痫发作衰减方面取得了成功，但它有一些风险，其机制仍然知之甚少。KD已显示改善癫痫表型中的代谢和线粒体功能。钾离子通道在癫痫病中具有重要意义，因为它们具有作为代谢传感器和控制神经元兴奋的双重作用。本研究的目的是探讨Kv1.1-KO癫痫模型海马和皮层组织脂质体的变化。FT-ICR/MS分析用于检查从癫痫Kv1.1通道敲除小鼠模型（n = 5）和野生型小鼠（n = 5）分离的皮层和海马组织的非极性代谢物组。观察到不同的代谢特征，海马中的显著（p < 0.05）特征通常被上调（FC ≥ 2）并且皮质被下调（FC ≤ 0.5）。途径富集分析显示脂质生物合成受到影响。分配比分析显示，大多数代谢物的比例在Kv1.1−/−中趋于增加。海马组织中的代谢物通常上调，表明癫痫发作在海马中启动。异常的线粒体功能与心磷脂（线粒体膜中的常见组分）的上调有关。总体而言，我们的研究发现，海马和皮质中的脂质体响应于Kv1.1-KO而改变，表明膜结构完整性和突触传递的变化。
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. The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy. 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). 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. 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.
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DOI：
10.1155/2011/303624
发表时间：
2011
期刊：
Epilepsy research and treatment
影响因子：
--
作者：
Kelly KM;Chung SS
通讯作者：
Chung SS
影响因子：
3.6
作者：
HUTTENLOCHER, PR
通讯作者：
HUTTENLOCHER, PR
影响因子：
3.5
作者：
Magrane, Jordi;Cortez, Czrina;Manfredi, Giovanni
通讯作者：
Manfredi, Giovanni
DOI：
10.1073/pnas.1308421110
发表时间：
2013-06-25
影响因子：
11.1
作者：
Dodge, James C.;Treleaven, Christopher M.;Shihabuddin, Lamya S.
通讯作者：
Shihabuddin, Lamya S.
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.