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难治性颞叶癫痫伴海马硬化患者的线粒体自噬。

Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis.

机构信息

Neurology Department, West China Hospital, Sichuan University, 37th Guoxuexiang Road, Chengdu, 610041, China.

State Key Laboratory of Biotherapy, West China Hospital and College of Life Sciences, Sichuan University, Chengdu, China.

出版信息

Cell Mol Neurobiol. 2018 Mar;38(2):479-486. doi: 10.1007/s10571-017-0492-2. Epub 2017 Apr 12.

Abstract

This study aimed to determine if there is an association between mitophagy and refractory temporal lobe epilepsy (rTLE) with hippocampal sclerosis. During epilepsy surgery, we collected tissue samples from the hippocampi and temporal lobe cortexes of rTLE patients with hippocampal sclerosis (as diagnosed by a pathologist). Transmission electron microscopy (TEM) was used to study the ultrastructural features of the tissue. To probe for mitophagy, we used fluorescent immunolabeling to determine if mitochondrial and autophagosomal markers colocalized. Fourteen samples were examined. TEM results showed that early autophagosomes were present and mitochondria were impaired to different degrees in hippocampi. Immunofluorescent labeling showed colocalization of the autophagosome marker LC3B with the mitochondrial marker TOMM20 in hippocampi and temporal lobe cortexes, indicating the presence of mitophagy. Mitochondrial and autophagosomal marker colocalization was lower in hippocampus than in temporal lobe cortex (P < 0.001). Accumulation of autophagosomes and mitophagy activation are implicated in rTLE with hippocampal sclerosis. Aberrant accumulation of damaged mitochondria, especially in the hippocampus, can be attributed to defects in mitophagy, which may participate in epileptogenesis.

摘要

这项研究旨在确定自噬与难治性颞叶癫痫(rTLE)伴海马硬化之间是否存在关联。在癫痫手术中,我们从 rTLE 伴海马硬化患者(由病理学家诊断)的海马和颞叶皮层中收集组织样本。使用透射电子显微镜(TEM)研究组织的超微结构特征。为了探测自噬,我们使用荧光免疫标记来确定线粒体和自噬体标记是否共定位。检查了 14 个样本。TEM 结果表明,早期自噬体存在,并且海马中线粒体受损程度不同。免疫荧光标记显示,自噬体标记 LC3B 与线粒体标记 TOMM20 在海马和颞叶皮层中存在共定位,表明存在自噬。与颞叶皮层相比,海马中线粒体和自噬体标记的共定位较低(P < 0.001)。自噬体和自噬激活的积累与伴海马硬化的 rTLE 有关。受损线粒体的异常积累,尤其是在海马中,可能归因于自噬缺陷,这可能参与了癫痫发生。

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