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.
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Acknowledgements
We thank Dr. Fang Zhao from the University of Helsinki for constructive comments on image analyses of TEM and fluorescent microscopy. We thank the patients and their families for their indispensable support. The study was financially supported by the National Natural Science Foundation of China (Grant No. 81571272).
Authors’ Contribution
MW—Study design, literature research, experimental studies, data acquisition, data analysis/interpretation, manuscript preparation, manuscript editing. XL—Study concepts, literature research, study design, data analysis. XC—Experimental studies, data analysis, statistical analysis. LZ—Experimental studies, data analysis. WX— Literature research, data analysis. SMVC—Data analysis/interpretation, manuscript editing. DZ—Study concepts, study design, manuscript revision. JL—Study concepts, study design, manuscript revision.
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Wu, M., Liu, X., Chi, X. et al. Mitophagy in Refractory Temporal Lobe Epilepsy Patients with Hippocampal Sclerosis. Cell Mol Neurobiol 38, 479–486 (2018). https://doi.org/10.1007/s10571-017-0492-2
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DOI: https://doi.org/10.1007/s10571-017-0492-2