Rescuing Kv10.2 protein changes cognitive and emotional function in kainic acid-induced status epilepticus rats

Liu, Yamei; Duan, Yi‐Shi; Du, Dongshu; Chen, Fuxue

doi:10.1016/j.yebeh.2019.106894

Cited by 9 publications

(6 citation statements)

References 25 publications

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“…However, these crucial genes were not involved in KEGG pathway-related regulation. Previous research has shown that three of the four key potassium channel genes (KCNA1, KCNA2, KCNJ11, and KCNS1) play vital roles in seizures and epilepsy (8)(9)(10). Four key potassium channel genes Lines are used to mark the position of members from the gene set in the gene sorting list, and the black line represents that the genes from the sorting gene table exist in the functional annotation gene set of the current analysis.…”

Section: Discussionmentioning

confidence: 99%

“…Potassium channels in cell membranes play a critical role in regulating neuronal excitability by controlling the transport of potassium ions across cells (4)(5)(6). Several potassium channels are associated with TLE, primarily based on animal experiments (7)(8)(9)(10). Research on the association between potassium levels and epilepsy may provide novel insights into the mechanisms and treatments of epilepsy.…”

Section: Introductionmentioning

confidence: 99%

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Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

et al. 2023

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One of the most prevalent types of epilepsy is temporal lobe epilepsy (TLE), which has unknown etiological factors and drug resistance. The detailed mechanisms underlying potassium channels in human TLE have not yet been elucidated. Hence, this study aimed to mine potassium channel genes linked to TLE using a bioinformatic approach. The results found that Four key TLE-related potassium channel genes (TERKPCGs) were identified: potassium voltage-gated channel subfamily E member (KCNA) 1, KCNA2, potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11), and KCNS1. A protein–protein interaction (PPI) network was constructed to analyze the relationship between TERKPCGs and other key module genes. The results of gene set enrichment analysis (GSEA) for a single gene indicated that the four TERKPCGs were highly linked to the cation channel, potassium channel, respiratory chain, and oxidative phosphorylation. The mRNA-TF network was established using four mRNAs and 113 predicted transcription factors. A ceRNA network containing seven miRNAs, two mRNAs, and 244 lncRNAs was constructed based on the TERKPCGs. Three common small-molecule drugs (enflurane, promethazine, and miconazole) target KCNA1, KCNA2, and KCNS1. Ten small-molecule drugs (glimepiride, diazoxide, levosimendan, and thiamylal et al.) were retrieved for KCNJ11. Compared to normal mice, the expression of KCNA1, KCNA2, KCNJ11, and KCNS1 was downregulated in the brain tissue of the epilepsy mouse model at both the transcriptional and translational levels, which was consistent with the trend of human data from the public database. The results indicated that key potassium channel genes linked to TLE were identified based on bioinformatics analysis to investigate the potential significance of potassium channel genes in the development and treatment of TLE.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

et al. 2023

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“…The variants in KCNH5 were associated with epilepsy ( Niday and Tzingounis, 2018 ). In epilepsy rats, upregulation of KCNH5 protein expression improved anxiety-like behavior and working memory ( Liu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis

Wang

Yang

et al. 2022

Front. Neurosci.

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ObjectiveTo investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues.MethodsBrain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS’ hippocampus and NTP’ cortex (data from our cohort). The strategy “Guilt by association” was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA.ResultsA significantly negative correlation (r < −0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network’s intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.

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“…Liu et al used a kainic acid (KA)-induced temporal lobe epilepsy model to examine the role of the Kv10.2 gene in status epilepticus (SE). The results indicated that anxiety-like behavior in rats increased after the injection of lentiviral plasmids containing the coding sequence region of the KCNH5 gene (LV-KCNH5) ( 14 ). Whole-exome sequencing (WES) is a powerful new tool for disease gene discovery.…”

Section: Discussionmentioning

confidence: 99%

Clinical Feature, Treatment, and KCNH5 Mutations in Epilepsy

Yang

Zhang

et al. 2022

Front. Pediatr.

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The voltage-gated Kv10.2 potassium channel, encoded by KCNH5, is broadly expressed in mammalian tissues, including the brain. Its potential mechanism remains unclear. According to previous studies, dysfunction of Kv10.2 may be associated with epileptic encephalopathies and autism spectrum disorder (ASD). To date, only one disease-causing mutation of KCNH5 has been reported, and it involves a case that presented with seizures and autism symptoms. In this study, we discovered and characterized three de novo mutations in KCNH5 that potentially caused severe conditions observed in three Chinese children. All of them experienced seizures, two of them presented with epileptic encephalopathy, one of them presented with ASD, and one did not relapse after drug withdrawal. Notably, treatment with antiepileptic drugs (AEDs) was effective in all patients whose epileptic seizures were controlled. The structures of the proteins resulting from the mutations were predicted in two of the three cases. This provides powerful insight into clinical heterogeneity and genotype-phenotype correlation in KCNH5-related diseases.

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Rescuing Kv10.2 protein changes cognitive and emotional function in kainic acid-induced status epilepticus rats

Cited by 9 publications

References 25 publications

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

Identification of key potassium channel genes of temporal lobe epilepsy by bioinformatics analyses and experimental verification

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis

Clinical Feature, Treatment, and KCNH5 Mutations in Epilepsy

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