Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis

Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis
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难治性颞叶癫痫合并海马硬化患者的线粒体自噬

DOI:
10.1007/s10571-017-0492-2
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发表时间:
2017-04
期刊:
Cell Mol Neurobiol
影响因子:
--
通讯作者:
李劲梅
李劲梅
中科院分区:
其他
文献类型:
--
作者:
李劲梅

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本研究旨在确定有丝分裂与难治性颞叶癫痫(RTLE)合并海马区硬化症之间是否存在关联。在癫痫手术期间,我们收集了经病理学家诊断的rTLE患者的海马区和颞叶皮质的组织样本。用透射电子显微镜观察组织的超微结构特征。为了探索有丝分裂,我们使用了荧光免疫标记来确定线粒体和自噬标记是否共定位。对14个样本进行了检测。透射电子显微镜结果显示,海马区存在早期自噬小体,线粒体有不同程度的损伤。免疫荧光标记显示自噬体标记物LC3B和线粒体标记物TOMM20在海马区和颞叶皮质共定位,表明存在有丝分裂。线粒体和自噬标记在海马区的共存低于在颞叶皮质(P<0.001)。自噬小体堆积和有丝分裂激活与rTLE合并海马区硬化有关。线粒体异常堆积,尤其是在海马区,可归因于线粒体吞噬缺陷,这可能参与癫痫的发生。
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.
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