Deciphering key regulators involved in epilepsy‐induced cardiac damage through whole transcriptome and proteome analysis in a rat model

Sharma, Supriya; Sharma, Meetal; Rana, Anil; Joshi, Robin; Swarnkar, Mohit Kumar; Acharya, Vishal; Singh, Damanpreet

doi:10.1111/epi.16794

Cited by 18 publications

(7 citation statements)

References 52 publications

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“…This rapidly appeared within minutes, while the major veins (inferior caval and superior mesenteric veins) appeared to be congested and the azygos vein failed. Furthermore, lithium may induce direct damage to the liver, kidneys [ 70 , 71 , 72 , 73 , 74 ], heart [ 75 , 76 ], lungs [ 77 , 78 ], and brain [ 79 , 80 ].…”

Section: Discussionmentioning

confidence: 99%

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

et al. 2021

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Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats.

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Section: Discussionmentioning

confidence: 99%

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

et al. 2021

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“…Epilepsy is a chronic recurrent transient brain dysfunction syndrome characterized by recurrent epileptic seizures, and with a high prevalence second to only that of stroke. Previous studies have focused on the molecular characterization of multiple homeostatic functions in tissue samples or cell populations, in which biological differences between cells can be obscured by averaging or being mistaken for technical noise 8,17 . However, the cell types in the same tissue can vary, resulting in unique dysregulated genes and functions.…”

Section: Discussionmentioning

confidence: 99%

“…Transcriptome analyses of epilepsy have been reported in several studies. [7][8][9] Dong et al 7 described the relationship between inflammation-related genes and cognitive dysfunction and epileptogenesis during drug administration for epilepsy, and they identified novel therapeutic targets for treating traumatic temporal lobe epilepsy (TLE) and its comorbidities. However, normal RNA-Seq only shows the whole picture of the transcriptome and reflects an average gene expression profile across heterogeneous populations of cells.…”

Section: Introductionmentioning

confidence: 99%

“…Transcriptome analyses of epilepsy have been reported in several studies. 7 , 8 , 9 Dong et al. 7 described the relationship between inflammation‐related genes and cognitive dysfunction and epileptogenesis during drug administration for epilepsy, and they identified novel therapeutic targets for treating traumatic temporal lobe epilepsy (TLE) and its comorbidities.…”

Section: Introductionmentioning

confidence: 99%

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Molecular mechanism analyses of post‐traumatic epilepsy and hereditary epilepsy based on 10× single‐cell transcriptome sequencing technology

Wen,

Tan,

Huang

et al. 2024

CNS Neurosci Ther

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BackgroundSingle‐cell RNA sequencing analysis has been usually conducted on post‐traumatic epilepsy (PET) and hereditary epilepsy (HE) patients; however, the transcriptome of patients with traumatic temporal lobe epilepsy has rarely been studied.Materials and MethodsHippocampus tissues isolated from one patient with PTE and one patient with HE were used in the present study. Single cell isolates were prepared and captured using a 10× Genomics Chromium Single‐Cell 3′ kit (V3) according to the manufacturer's instructions. The libraries were sequenced on an Illumina NovaSeq 6000 sequencing system. Raw data were processed, and the cells were filtered and classified using the Seurat R package. Uniform Manifold Approximation and Projection was used for visualization. Differentially expressed genes (DEGs) were identified based on a p‐value ≤0.01 and log fold change (FC) ≥0.25. Gene Ontology (GO, http://geneontology.org/) and KEGG (Kyoto Encyclopedia of Genes and Genomes, www.genome.jp/kegg) analyses were performed on the DEGs for enrichment analysis.ResultsThe reads obtained from the 10× genomic platform for PTE and HE were 39.56 M and 30.08 M, respectively. The Q30 score of the RNA reads was >91.6%. After filtering, 7479 PTE cells and 9357 HE cells remained for further study. More than 96.4% of the reads were mapped to GRCh38/GRCm38. The cells were differentially distributed in two groups, with higher numbers of oligodendrocytes (6522 vs. 2532) and astrocytes (133 vs. 52), and lower numbers of microglial cells (2242 vs. 3811), and neurons (3 vs. 203) present in the HE group than in the PTE group. The DEGs in four cell clusters were identified, with 25 being in oligodendrocytes (13 upregulated and 12 downregulated), 87 in microglia cells (42 upregulated and 45 downregulated), 222 in astrocytes (115 upregulated and 107 downregulated), and 393 in neurons (305 upregulated and 88 downregulated). The genes MTND1P23 (downregulated), XIST (downregulated), and RPS4Y1 (upregulated) were commonly expressed in all four cell clusters. The DEGs in microglial cells and astrocytes were enriched in the IL‐17 signaling pathway.ConclusionOur study explored differences in cells found in a patient with PE compared to a patient with HE, and the transcriptome in the different cells was analyzed for the first time. Studying inflammatory and immune functions might be the best approach for investigating traumatic temporal lobe epilepsy in neurons.

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“…The combined proteomics and transcriptomics analysis are now also commonly used in the field of epilepsy. Several academics have identified key regulators involved in epilepsy-induced cardiac injury via combined proteomics and transcriptomics analysis ( Sharma et al, 2021 ). Nevertheless, there is no research to apply this combination of both in the field of epilepsy ( Shan et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Combined transcriptomics and proteomics forecast analysis for potential biomarker in the acute phase of temporal lobe epilepsy

Cong

You

et al. 2023

Front. Neurosci.

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BackgroundTemporal lobe epilepsy (TLE) is a common chronic episodic illness of the nervous system. However, the precise mechanisms of dysfunction and diagnostic biomarkers in the acute phase of TLE are uncertain and hard to diagnose. Thus, we intended to qualify potential biomarkers in the acute phase of TLE for clinical diagnostics and therapeutic purposes.MethodsAn intra-hippocampal injection of kainic acid was used to induce an epileptic model in mice. First, with a TMT/iTRAQ quantitative labeling proteomics approach, we screened for differentially expressed proteins (DEPs) in the acute phase of TLE. Then, differentially expressed genes (DEGs) in the acute phase of TLE were identified by linear modeling on microarray data (limma) and weighted gene co-expression network analysis (WGCNA) using the publicly available microarray dataset GSE88992. Co-expressed genes (proteins) in the acute phase of TLE were identified by overlap analysis of DEPs and DEGs. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were used to screen Hub genes in the acute phase of TLE, and logistic regression algorithms were applied to develop a novel diagnostic model for the acute phase of TLE, and the sensitivity of the diagnostic model was validated using receiver operating characteristic (ROC) curves.ResultsWe screened a total of 10 co-expressed genes (proteins) from TLE-associated DEGs and DEPs utilizing proteomic and transcriptome analysis. LASSO and SVM-RFE algorithms for machine learning were applied to identify three Hub genes: Ctla2a, Hapln2, and Pecam1. A logistic regression algorithm was applied to establish and validate a novel diagnostic model for the acute phase of TLE based on three Hub genes in the publicly accessible datasets GSE88992, GSE49030, and GSE79129.ConclusionOur study establishes a reliable model for screening and diagnosing the acute phase of TLE that provides a theoretical basis for adding diagnostic biomarkers for TLE acute phase genes.

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Deciphering key regulators involved in epilepsy‐induced cardiac damage through whole transcriptome and proteome analysis in a rat model

Cited by 18 publications

References 52 publications

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

Molecular mechanism analyses of post‐traumatic epilepsy and hereditary epilepsy based on 10× single‐cell transcriptome sequencing technology

Combined transcriptomics and proteomics forecast analysis for potential biomarker in the acute phase of temporal lobe epilepsy

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