Cargando…
The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells
Epilepsy is the most common childhood neurologic disorder. Status epilepticus (SE), which refers to continuous epileptic seizures, occurs more frequently in children than in adults, and approximately 40–50% of all cases occur in children under 2 years of age. Conventional antiepileptic drugs current...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550833/ https://www.ncbi.nlm.nih.gov/pubmed/34721570 http://dx.doi.org/10.1155/2021/7174287 |
_version_ | 1784591038534385664 |
---|---|
author | Xie, RuiJin Li, TianXiao Qiao, XinYu Mei, HuiYa Hu, GuoQin Li, LongFei Sun, Chenyu Cheng, Ce Cui, Yin Hong, Ni Liu, Yueying |
author_facet | Xie, RuiJin Li, TianXiao Qiao, XinYu Mei, HuiYa Hu, GuoQin Li, LongFei Sun, Chenyu Cheng, Ce Cui, Yin Hong, Ni Liu, Yueying |
author_sort | Xie, RuiJin |
collection | PubMed |
description | Epilepsy is the most common childhood neurologic disorder. Status epilepticus (SE), which refers to continuous epileptic seizures, occurs more frequently in children than in adults, and approximately 40–50% of all cases occur in children under 2 years of age. Conventional antiepileptic drugs currently used in clinical practice have a number of adverse side effects. Drug-resistant epilepsy (DRE) can progressively develop in children with persistent SE, necessitating the development of novel therapeutic drugs. During SE, the persistent activation of neurons leads to decreased glutamate clearance with corresponding glutamate accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Our previous study demonstrated that after developmental seizures in rats, E-64d exerts a neuroprotective effect on the seizure-induced brain damage by modulating lipid metabolism enzymes, especially ApoE and ApoJ/clusterin. In this study, we investigated the impact and mechanisms of E-64d administration on neuronal excitotoxicity. To test our hypothesis that E-64d confers neuroprotective effects by regulating autophagy and mitochondrial pathway activity, we simulated neuronal excitotoxicity in vitro using an immortalized hippocampal neuron cell line (HT22). We found that E-64d improved cell viability while reducing oxidative stress and neuronal apoptosis. In addition, E-64d treatment regulated mitochondrial pathway activity and inhibited chaperone-mediated autophagy in HT22 cells. Our findings indicate that E-64d may alleviate glutamate-induced damage via regulation of mitochondrial fission and apoptosis, as well as inhibition of chaperone-mediated autophagy. Thus, E-64d may be a promising therapeutic treatment for hippocampal injury associated with SE. |
format | Online Article Text |
id | pubmed-8550833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-85508332021-10-28 The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells Xie, RuiJin Li, TianXiao Qiao, XinYu Mei, HuiYa Hu, GuoQin Li, LongFei Sun, Chenyu Cheng, Ce Cui, Yin Hong, Ni Liu, Yueying Neural Plast Research Article Epilepsy is the most common childhood neurologic disorder. Status epilepticus (SE), which refers to continuous epileptic seizures, occurs more frequently in children than in adults, and approximately 40–50% of all cases occur in children under 2 years of age. Conventional antiepileptic drugs currently used in clinical practice have a number of adverse side effects. Drug-resistant epilepsy (DRE) can progressively develop in children with persistent SE, necessitating the development of novel therapeutic drugs. During SE, the persistent activation of neurons leads to decreased glutamate clearance with corresponding glutamate accumulation in the synaptic extracellular space, increasing the chance of neuronal excitotoxicity. Our previous study demonstrated that after developmental seizures in rats, E-64d exerts a neuroprotective effect on the seizure-induced brain damage by modulating lipid metabolism enzymes, especially ApoE and ApoJ/clusterin. In this study, we investigated the impact and mechanisms of E-64d administration on neuronal excitotoxicity. To test our hypothesis that E-64d confers neuroprotective effects by regulating autophagy and mitochondrial pathway activity, we simulated neuronal excitotoxicity in vitro using an immortalized hippocampal neuron cell line (HT22). We found that E-64d improved cell viability while reducing oxidative stress and neuronal apoptosis. In addition, E-64d treatment regulated mitochondrial pathway activity and inhibited chaperone-mediated autophagy in HT22 cells. Our findings indicate that E-64d may alleviate glutamate-induced damage via regulation of mitochondrial fission and apoptosis, as well as inhibition of chaperone-mediated autophagy. Thus, E-64d may be a promising therapeutic treatment for hippocampal injury associated with SE. Hindawi 2021-10-20 /pmc/articles/PMC8550833/ /pubmed/34721570 http://dx.doi.org/10.1155/2021/7174287 Text en Copyright © 2021 RuiJin Xie et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Xie, RuiJin Li, TianXiao Qiao, XinYu Mei, HuiYa Hu, GuoQin Li, LongFei Sun, Chenyu Cheng, Ce Cui, Yin Hong, Ni Liu, Yueying The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells |
title | The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells |
title_full | The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells |
title_fullStr | The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells |
title_full_unstemmed | The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells |
title_short | The Protective Role of E-64d in Hippocampal Excitotoxic Neuronal Injury Induced by Glutamate in HT22 Hippocampal Neuronal Cells |
title_sort | protective role of e-64d in hippocampal excitotoxic neuronal injury induced by glutamate in ht22 hippocampal neuronal cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8550833/ https://www.ncbi.nlm.nih.gov/pubmed/34721570 http://dx.doi.org/10.1155/2021/7174287 |
work_keys_str_mv | AT xieruijin theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT litianxiao theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT qiaoxinyu theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT meihuiya theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT huguoqin theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT lilongfei theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT sunchenyu theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT chengce theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT cuiyin theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT hongni theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT liuyueying theprotectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT xieruijin protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT litianxiao protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT qiaoxinyu protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT meihuiya protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT huguoqin protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT lilongfei protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT sunchenyu protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT chengce protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT cuiyin protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT hongni protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells AT liuyueying protectiveroleofe64dinhippocampalexcitotoxicneuronalinjuryinducedbyglutamateinht22hippocampalneuronalcells |