PGC-1α Affects Epileptic Seizures by Regulating Mitochondrial Fusion in Epileptic Rats

Li, Dongxu; Zhang, Linhai; Tuo, Jinmei; Zhang, Fan; Tai, Zhenzhen; Liu, Xiping; Qiu, Xiaowei; Zhang, Haiqing; Yang, Juan; Wang, Jing; Luo, Zhong; Zhou, Xu

doi:10.1007/s11064-022-03834-3

Cited by 6 publications

(1 citation statement)

References 35 publications

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“…They produce nearly 95% of the cellular adenosine triphosphate (ATP) through oxidative phosphorylation 3 . Mitochondrial dynamics is a dynamic process in which mitochondria fuse and split to form small, circular organelles or join together to form tubular networks to meet the energy metabolism needs of the cell 4,5 . The release of adenosine, one of the ATP degradation products, from glial cells and synaptic vesicles is reduced by excessive mitochondrial ssion, which limits the hyperexcitability of neurons 6 .…”

Section: Introductionmentioning

confidence: 99%

ERK1/2 regulates Epileptic Seizures by modulating the DRP1 mediated Mitochondrial Dynamic

Chen,

Yang,

Zheng

et al. 2023

Preprint

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Objective: After seizures, the hyperactivation of Extracellular signal-regulated kinases (ERK1/2) causes dysfunction of mitochondrial. Through the guideline of Dynamin-related protein 1（DRP1）, ERK1/2 plays a role in the pathogenesis of several illnesses, for instance cancer, Parkinson's, and Alzheimer's. However, it is unclear whether DRP1 function is regulated by ERK1/2 in the pathogenesis of seizures. Method: LiCl-Pilocarpine was injected intraperitoneally to establish a status epilepticus (SE) rat for this study. Before SE induction, PD98059 and Mdivi-1 were injected intraoperatively. The number of seizures and the latency of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in hippocampal neurons CA1 and CA3. Results: Both PD98059 and Mdivi-1 reduced rats' susceptibility to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced p-DRP1 expression level at the Ser616. Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Conclusions: p-DRP1-Ser616 expression, which may regulate the pathogenesis of epilepsy by inhibiting DRP1-mediated excessive mitochondrial fission, is downregulated when ERK1/2 signaling pathways are inhibited.

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Section: Introductionmentioning

confidence: 99%

ERK1/2 regulates Epileptic Seizures by modulating the DRP1 mediated Mitochondrial Dynamic

Chen,

Yang,

Zheng

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1‐Mediated Mitochondrial Dynamic

Chen,

Yang,

Zheng

et al. 2024

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After seizures, the hyperactivation of extracellular signal‐regulated kinases (ERK1/2) causes mitochondrial dysfunction. Through the guidance of dynamin‐related protein 1 (DRP1), ERK1/2 plays a role in the pathogenesis of several illnesses. Herein, we speculate that ERK1/2 affects mitochondrial division and participates in the pathogenesis of epilepsy by regulating the activity of DRP1. LiCl‐Pilocarpine was injected intraperitoneally to establish a rat model of status epilepticus (SE) for this study. Before SE induction, PD98059 and Mdivi‐1 were injected intraperitoneally. The number of seizures and the latency period before the onset of the first seizure were then monitored. The analysis of Western blot was also used to measure the phosphorylated and total ERK1/2 and DRP1 protein expression levels in the rat hippocampus. In addition, immunohistochemistry revealed the distribution of ERK1/2 and DRP1 in neurons of hippocampal CA1 and CA3. Both PD98059 and Mdivi‐1 reduced the susceptibility of rats to epileptic seizures, according to behavioral findings. By inhibiting ERK1/2 phosphorylation, the Western blot revealed that PD98059 indirectly reduced the phosphorylation of DRP1 at Ser616 (p‐DRP1‐Ser616). Eventually, the ERK1/2 and DRP1 were distributed in the cytoplasm of neurons by immunohistochemistry. Inhibition of ERK1/2 signaling pathways downregulates p‐DRP1‐Ser616 expression, which could inhibit DRP1‐mediated excessive mitochondrial fission and then regulate the pathogenesis of epilepsy.

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AMPK role in epilepsy: a promising therapeutic target?

Qi,

Zhang,

Gao

et al. 2023

J Neurol

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PGC-1α Affects Epileptic Seizures by Regulating Mitochondrial Fusion in Epileptic Rats

Cited by 6 publications

References 35 publications

ERK1/2 regulates Epileptic Seizures by modulating the DRP1 mediated Mitochondrial Dynamic

ERK1/2 regulates Epileptic Seizures by modulating the DRP1 mediated Mitochondrial Dynamic

ERK1/2 Regulates Epileptic Seizures by Modulating the DRP1‐Mediated Mitochondrial Dynamic

AMPK role in epilepsy: a promising therapeutic target?

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