Dataset Information

Identification of MicroRNA-Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy.

ABSTRACT: Background: Dysregulated expression of microRNAs and potassium channels have been reported for their contributions to seizure onset. However, the microRNA-potassium channel gene interactions in traumatic brain injury-induced post-traumatic epilepsy (PTE) remain unknown. Methods: PTE was induced in male rats by intracranial injection with ferrous chloride (0.1 mol/L, 1 ?l/min) at the right frontal cortex. Electroencephalography was recorded at 60 min, as well as day 1, 7, and 30, and the behavioral seizures were assessed before injection and at different time points after injection. Rats were killed on day 30 after injection. The right frontal cortex samples were collected and subjected to high throughput messenger RNA (mRNA) and microRNA sequencing. A network of differentially expressed potassium channel mRNAs and microRNAs was constructed using OryCun2.0 and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The differential mRNA and microRNA expressions were verified using quantitative real-time-PCR. The microRNA-mRNA was subject to the Pearson correlation analysis. Results: A PTE rat model was successfully established, as evidenced by behavioral seizures and epileptiform discharges on electroencephalography in PTE rats compared with sham rats. Among the 91 mRNAs and 40 microRNAs that were significantly differentially expressed in the PTE rat brain, 4 mRNAs and 10 microRNAs were associated with potassium channels. Except for potassium calcium-activated channel subfamily N member 2, the other three potassium channel mRNAs were negatively correlated with seven microRNAs. These microRNA-mRNA pairs were enriched in annotations and pathways related to neuronal ion channels and neuroinflammation. Quantitative real-time-PCR and correlation analysis verified negative correlations in miR-449a-5p-KCNH2, miR-98-5p-KCNH2, miR-98-5p-KCNK15, miR-19b-3p-KCNK15, and miR-301a-3p-KCNK15 pairs. Conclusion: We identified microRNA-potassium channel mRNA interactions associated with PTE, providing potential diagnostic markers and therapeutic targets for PTE.

SUBMITTER: Li Z

PROVIDER: S-EPMC7882489 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification of MicroRNA-Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy.

Li Zheng Z Ma Yixun Y Zhou Fengjuan F Jia Xiao X Zhan Jingjing J Tan Huachao H Wang Xu X Yang Tiantong T Liu Quan Q

Frontiers in molecular neuroscience 20210201

<b>Background:</b> Dysregulated expression of microRNAs and potassium channels have been reported for their contributions to seizure onset. However, the microRNA-potassium channel gene interactions in traumatic brain injury-induced post-traumatic epilepsy (PTE) remain unknown. <b>Methods:</b> PTE was induced in male rats by intracranial injection with ferrous chloride (0.1 mol/L, 1 μl/min) at the right frontal cortex. Electroencephalography was recorded at 60 min, as well as day 1, 7, and 30, an ...[more]

PMID: 33597846

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Project description:IntroductionPost-traumatic epilepsy (PTE) is a recognised complication of traumatic brain injury (TBI), and is associated with higher rates of mortality and morbidity when compared with patients with TBI who do not develop PTE. The majority of the literature on PTE has focused on adult populations, and consequently there is a paucity of information regarding paediatric cohorts. Additionally, there is considerable heterogeneity surrounding the reported incidence of PTE following childhood TBI in the current literature. The primary aim of our study is to summarise reported PTE incidences in paediatric populations to derive an accurate estimate of the global incidence of PTE following childhood TBI. Our secondary aim is to explore risk factors that increase the likelihood of developing PTE.Methods and analysisA systematic literature search of Embase (1947-2021), PubMed (1996-2021) and Web of Science (1900-2021) will be conducted. Publications in English that report the incidence of PTE in populations under 18 years of age will be included. Publications that evaluate fewer than 10 patients, report an alternative cause of epilepsy, or in which a paediatric cohort is not discernable, will be excluded. Independent investigators will identify the relevant publications, and discrepancies will be adjudicated by a third independent investigator. Data extracted will include incidence of PTE, time intervals between TBI and PTE, seizure characteristics, injury characteristics, patient demographics and clinical data. Data extraction will be performed by two independent investigators and cross-checked by a third investigator. A descriptive analysis of PTE incidence will be conducted and a weighted mean will be calculated. If sufficient data are available, stratified meta-analysis of subgroups will also be conducted.Ethics and disseminationEthics approval was not required for this study. We intend to publish our findings in a high-quality peer-reviewed journal on completion.Prospero registration numberCRD42021245802.

Project description:BackgroundGlutamate is one of the most important excitatory neurotransmitters in the mammalian brain and is involved in a variety of neurological disorders. Increasing evidence also shows that microRNA (miRNA) and mRNA pairs are engaged in a variety of pathophysiological processes. However, the miRNA and mRNA pairs that affect the glutamatergic system in post-traumatic epilepsy (PTE) remain unknown.MethodsPTE rats were induced by injecting 0.1 mol/L, 1 μL/min FeCl2 solution. Behavioral scores and EEG monitoring were used to evaluate whether PTE was successfully induced. RNA-seq was used to obtain mRNA and miRNA expression profiles. Bioinformatics analysis was performed to screen differentially expressed mRNAs and miRNAs associated with the glutamatergic system and then predict miRNA-mRNA interaction pairs. Real-time quantitative reverse transcription PCR was used to further validate the expression of the differential miRNAs and mRNAs. The microRNA-mRNA was subject to the Pearson correlation analysis.ResultsEight of the 91 differentially expressed mRNAs were associated with the glutamatergic system, of which six were upregulated and two were downregulated. Forty miRNAs were significantly differentially expressed, with 14 upregulated and 26 downregulated genes. The predicted miRNA-mRNA interaction network shows that five of the eight differentially expressed mRNAs associated with the glutamatergic system were targeted by multiple miRNAs, including Slc17a6, Mef2c, Fyn, Slc25a22, and Shank2, while the remaining three mRNAs were not targeted by any miRNAs. Of the 40 differentially expressed miRNAs, seven miRNAs were found to have multiple target mRNAs associated with the glutamatergic system. Real-time quantitative reverse transcription PCR validation and Pearson correlation analysis were performed on these seven targeted miRNAs-Slc17a6, Mef2c, Fyn, Slc25a22, and Shank2-and six additional miRNAs selected from the literature. Real-time quantitative reverse transcription PCR showed that the expression levels of the mRNAs and miRNAs agreed with the predictions in the study. Among them, the miR-98-5p-Slc17a6, miR-335-5p-Slc17a6, miR-30e-5p-Slc17a6, miR-1224-Slc25a22, and miR-211-5p-Slc25a22 pairs were verified to have negative correlations.ConclusionsOur results indicate that miRNA-mRNA interaction pairs associated with the glutamatergic system are involved in the development of PTE and have potential as diagnostic biomarkers and therapeutic targets for PTE.

Dataset Information

Identification of MicroRNA-Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy.

Publications

Identification of MicroRNA-Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy.

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