Open AccessParthanatos participates in glutamate‐mediated HT22 cell injury and hippocampal neuronal death in kainic acid‐induced status epilepticus rats
Author(s) -
Wang Xue,
Zhang Wuqiong,
Ge Pengfei,
Yu Miaomiao,
Meng Hongmei
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13934
Subject(s) - programmed cell death , glutamate receptor , excitotoxicity , status epilepticus , hippocampal formation , kainic acid , biology , microbiology and biotechnology , cell damage , poly adp ribose polymerase , pharmacology , neuroscience , epilepsy , apoptosis , biochemistry , polymerase , receptor , gene
Aims Epileptic seizures or status epilepticus (SE) can cause hippocampal neuronal death, which has detrimental effects. Parthanatos, a new form of programmed cell death, is characterized by hyperactivation of poly (ADP‐ribose) polymerase‐1 (PARP‐1), excessive synthesis of poly ADP‐ribose polymer, mitochondrial depolarization, and nuclear translocation of apoptosis‐inducing factor, observed in various neurodegenerative disorders but rarely reported in epilepsy. We aimed to investigate whether parthanatos participates in the mechanism of seizure‐induced hippocampal neuronal death. Methods Glutamate‐mediated excitotoxicity cell model was used to study the mechanism of seizure‐induced cell injury. Injection of kainic acid into the amygdala was used to establish the epileptic rat model. Corresponding biochemical tests were carried out on hippocampal tissues and HT22 cells following indicated treatments. Results In vitro, glutamate time‐dependently induced HT22 cell death, accompanied by parthanatos‐related biochemical events. Pretreatment with PJ34 (PARP‐1 inhibitor) or small interfering RNA‐mediated PARP‐1 knockdown effectively protected HT22 cells against glutamate‐induced toxic effects and attenuated parthanatos‐related biochemical events. Application of the antioxidant N‐acetylcysteine (NAC) rescued HT22 cell death and reversed parthanatos‐related biochemical events. In vivo, PJ34 and NAC afforded protection against SE‐induced hippocampal neuronal damage and inhibited parthanatos‐related biochemical events. Conclusion Parthanatos participates in glutamate‐induced HT22 cell injury and hippocampal neuronal damage in rats following epileptic seizures. ROS might be the initiating factor during parthanatos.