Study of Neuronal Apoptosis ceRNA Network in Hippocampal Sclerosis of Human Temporal Lobe Epilepsy by RNA-Seq

Hippocampal sclerosis (HS) is one of the most common pathological type of intractable temporal lobe epilepsy (TLE), often characterized by hippocampal atrophy, neuronal apoptosis, and gliogenesis. However, the molecular mechanisms of neuronal apoptosis in patients with HS are still not fully understood. We therefore conducted a pilot study focusing on the neuronal apoptosis ceRNA network in the sclerotic hippocampus of intractable TLE patients. In this research, RNA sequencing (RNA-seq) was utilized to quantify the expression levels of lncRNAs, miRNAs, and mRNAs in TLE patients with HS (HS-TLE) and without HS (non-HS-TLE), and reverse transcription-quantitative PCR (qRT-PCR). The interactions of differential expression (DE) lncRNAs-miRNAs or DEmiRNAs-mRNAs were integrated by StarBase v3.0, and visualized using Cytoscape. Subsequently, we annotate the functions of lncRNA-associated competitive endogenous RNA (ceRNA) network through analysis of their interactions with mRNAs. RNA-seq analyses showed 381 lncRNAs, 42 miRNAs, and 457 mRNAs were dysregulated expression in HS-TLE compared to non-HS-TLE. According to the ceRNA hypothesis, 5 HS-specific ceRNA network were constructed. Among them, the core ceRNA regulatory network involved in neuronal apoptosis was constituted by 10 DElncRNAs (CDKN2B-AS1, MEG3, UBA6-AS1, etc.), 7 DEmiRNAs (hsa-miR-155-5p, hsa-miR-195-5p, hsa-miR-200c-3p, etc.), and 3 DEmRNAs (SCN2A, DYRK2, and MAPK8), which belonging to apoptotic and epileptic terms. Our findings established the first ceRNA network of lncRNA-mediated neuronal apoptosis in HS-TLE based on transcriptome sequencing, which provide a new perspective on the disease pathogenesis and precise treatments of HS.

Download Full-text

Transcriptome analysis reveals higher levels of mobile element-associated abnormal gene transcripts in temporal lobe epilepsy patients

10.1101/2021.05.14.444199 ◽

2021 ◽

Author(s):

Hai Hu ◽

Ping Liang

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Molecular Mechanisms ◽

De Novo ◽

Splice Variants ◽

Transcriptome Assembly ◽

Hippocampal Sclerosis ◽

Mobile Element ◽

Loss Of Function ◽

Gene Transcripts

Objective: To determine role of abnormal splice variants associated with mobile elements in epilepsy. Methods: Publicly available human RNA-seq-based transcriptome data for laser-captured dentate granule cells of post-mortem hippocampal tissues from temporal lobe epilepsy patients with (TLE, N=14 for 7 subjects) and without hippocampal sclerosis (TLE-HS, N=8 for 5 subjects) and healthy individuals (N=51), surgically resected bulk neocortex tissues from TLE patients (TLE-NC, N=17). For each individual sample, de novo transcriptome assembly was performed followed by identification of spliced gene transcripts containing mobile element (ME) sequences (ME-transcripts) to compare the ME-transcript frequency across the sample groups. Enrichment analysis for genes associated with ME-transcripts and detailed sequence examination for representative epileptic genes were performed to analyze the pattern and mechanism of ME-transcripts on gene function. Results: We observed significantly higher levels of ME-transcripts in the hippocampal tissues of epileptic patients, particularly in TLE-HS. Among ME classes, SINEs were shown to be the most frequent contributor to ME-transcripts followed by LINEs and DNA transposons. These ME sequences almost in all cases represent older MEs normally located in the intron sequences, leading abnormal splicing variants. For protein coding genes, ME sequences were mostly found in the 3-UTR regions, with a significant portion also in the coding sequences (CDS) leading to reading frame disruption. Genes associated with ME-transcripts showed enrichment for involvement in the mRNA splicing process in all sample groups, with bias towards neural and epilepsy-associated genes in the epileptic transcriptomes. Significance: Our data suggest that abnormal splicing involving MEs, leading to loss of function in critical genes, plays a role in epilepsy, particularly in TLE-HS, providing a novel insight on the molecular mechanisms underlying epileptogenesis.

Download Full-text

Transcriptomic analysis of the subiculum region of the hippocampus in animals with temporal lobe epilepsy (ELTM) induced by pilocarpine

Revista dos Trabalhos de Iniciação Científica da UNICAMP ◽

10.20396/revpibic262018191 ◽

2018 ◽

Author(s):

Beatriz Bertelli Aoyama ◽

Andre Schwambach Vieira ◽

Amanda Morato do Canto ◽

Alexandre Hilário Berenguer ◽

Benilton de Sá Carvalho ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Rna Sequencing ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Classical Model ◽

Mesial Temporal Lobe Epilepsy ◽

Rna Seq ◽

Mesial Temporal Lobe ◽

Histopathological Lesion

Mesial temporal lobe epilepsy (MTLE) is the most frequent type of epilepsy in adults and it is usually refractory to clinical treatments. In most patients with MTLE a characteristic histopathological lesion is observed, including hippocampal sclerosis (HS). The subiculum is an important area which connects the hippocampus with the enthorrinal cortex. In this study aims to understand the molecular role of the subiculum in MTLE in the classical model of pilocarpine using RNA-seq (RNA sequencing)

Download Full-text

iTRAQ-Based Proteomic Analysis of Dentate Gyrus in Temporal Lobe Epilepsy With Hippocampal Sclerosis

Frontiers in Neurology ◽

10.3389/fneur.2020.626013 ◽

2021 ◽

Vol 11 ◽

Author(s):

Wenbiao Xiao ◽

Zhiquan Yang ◽

Xiaoxin Yan ◽

Li Feng ◽

Lili Long ◽

...

Keyword(s):

Oxidative Phosphorylation ◽

Temporal Lobe Epilepsy ◽

Dentate Gyrus ◽

Temporal Lobe ◽

Molecular Mechanisms ◽

Focal Epilepsy ◽

Hippocampal Sclerosis ◽

Interaction Network ◽

Absolute Quantitation ◽

Functional Changes

Temporal lobe epilepsy (TLE) is the most frequent type of focal epilepsy in adults, typically resistant to pharmacological treatment, and mostly presents with cognitive impairment and psychiatric comorbidities. The most common neuropathological hallmark in TLE patients is hippocampal sclerosis (HS). However, the underlying molecular mechanisms involved remain poorly characterized. The dentate gyrus (DG), one specific hippocampal subarea, structural and functional changes imply a key involvement of the DG in the development of TLE. In this study, a isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technique was performed for the analysis of hippocampal DG obtained from patients with TLE-HS compared to control samples obtained from autopsy. Our proteomic data identified 5,583 proteins, of which 82 proteins were upregulated and 90 proteins were downregulated. Bioinformatics analysis indicated that differentially expressed proteins were enriched in “synaptic vesicle,” “mitochondrion,” “cell-cell adhesion,” “regulation of synaptic plasticity,” “ATP binding,” and “oxidative phosphorylation.” Protein-protein interaction network analysis found a pivotal module of 10 proteins that were related to “oxidative phosphorylation.” This study has investigated proteomic alterations in the DG region of TLE-HS patients, and paved the way for the better understanding of epileptogenesis mechanisms and future therapeutic intervention.

Download Full-text

Faculty Opinions recommendation of Optimized SEEG-guided radiofrequency thermocoagulation for mesial temporal lobe epilepsy with hippocampal sclerosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736604573.793566615 ◽

2019 ◽

Author(s):

John Paul Leach

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Mesial Temporal Lobe Epilepsy ◽

Radiofrequency Thermocoagulation ◽

Mesial Temporal Lobe

Download Full-text

Synaptic Reshaping and Neuronal Outcomes in the Temporal Lobe Epilepsy

International Journal of Molecular Sciences ◽

10.3390/ijms22083860 ◽

2021 ◽

Vol 22 (8) ◽

pp. 3860

Author(s):

Elisa Ren ◽

Giulia Curia

Keyword(s):

Animal Models ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Current Knowledge ◽

Focal Epilepsy ◽

Ex Vivo ◽

Hippocampal Sclerosis ◽

Control Group ◽

Epileptogenic Zone ◽

Epileptiform Discharges

Temporal lobe epilepsy (TLE) is one of the most common types of focal epilepsy, characterized by recurrent spontaneous seizures originating in the temporal lobe(s), with mesial TLE (mTLE) as the worst form of TLE, often associated with hippocampal sclerosis. Abnormal epileptiform discharges are the result, among others, of altered cell-to-cell communication in both chemical and electrical transmissions. Current knowledge about the neurobiology of TLE in human patients emerges from pathological studies of biopsy specimens isolated from the epileptogenic zone or, in a few more recent investigations, from living subjects using positron emission tomography (PET). To overcome limitations related to the use of human tissue, animal models are of great help as they allow the selection of homogeneous samples still presenting a more various scenario of the epileptic syndrome, the presence of a comparable control group, and the availability of a greater amount of tissue for in vitro/ex vivo investigations. This review provides an overview of the structural and functional alterations of synaptic connections in the brain of TLE/mTLE patients and animal models.

Download Full-text

Comprehensive analysis of competitive endogenous RNA associated with immune infiltration in lung adenocarcinoma

Scientific Reports ◽

10.1038/s41598-021-90755-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenjie Chen ◽

Wen Li ◽

Zhenkun Liu ◽

Guangzhi Ma ◽

Yunfu Deng ◽

...

Keyword(s):

Prognostic Factors ◽

Mast Cells ◽

Correlation Analysis ◽

Lung Adenocarcinoma ◽

Molecular Mechanisms ◽

Cox Regression ◽

The Cancer Genome Atlas ◽

Cerna Network ◽

Monocytes And Macrophages ◽

Competitive Endogenous Rna

AbstractTo identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan–Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.

Download Full-text

Stereotactic EEG-guided radiofrequency thermocoagulation versus anterior temporal lobectomy for mesial temporal lobe epilepsy with hippocampal sclerosis: study protocol for a randomised controlled trial

Trials ◽

10.1186/s13063-021-05378-3 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Yi-He Wang ◽

Si-Chang Chen ◽

Peng-Hu Wei ◽

Kun Yang ◽

Xiao-Tong Fan ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Hippocampal Sclerosis ◽

Controlled Trial ◽

Mesial Temporal Lobe Epilepsy ◽

Temporal Lobectomy ◽

Anterior Temporal Lobectomy ◽

Radiofrequency Thermocoagulation ◽

Mesial Temporal Lobe ◽

Randomised Controlled

Abstract Introduction In this report, we aim to describe the design for the randomised controlled trial of Stereotactic electroencephalogram (EEG)-guided Radiofrequency Thermocoagulation versus Anterior Temporal Lobectomy for Mesial Temporal Lobe Epilepsy with Hippocampal Sclerosis (STARTS). Mesial temporal lobe epilepsy (mTLE) is a classical subtype of temporal lobe epilepsy that often requires surgical intervention. Although anterior temporal lobectomy (ATL) remains the most popular treatment for mTLE, accumulating evidence has indicated that ATL can cause tetartanopia and memory impairments. Stereotactic EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) is a non-invasive alternative associated with lower seizure freedom but greater preservation of neurological function. In the present study, we aim to compare the safety and efficacy of SEEG-guided RF-TC and classical ATL in the treatment of mTLE. Methods and analysis STARTS is a single-centre, two-arm, randomised controlled, parallel-group clinical trial. The study includes patients with typical mTLE over the age of 14 who have drug-resistant seizures for at least 2 years and have been determined via detailed evaluation to be surgical candidates prior to randomisation. The primary outcome measure is the cognitive function at the 1-year follow-up after treatment. Seizure outcomes, visual field abnormalities after surgery, quality of life, ancillary outcomes, and adverse events will also be evaluated at 1-year follow-up as secondary outcomes. Discussion SEEG-guided RF-TC for mTLE remains a controversial seizure outcome but has the advantage for cognitive and visual field protection. This is the first RCT studying cognitive outcomes and treatment results between SEEG-guided RF-TC and standard ATL for mTLE with hippocampal sclerosis. This study may provide higher levels of clinical evidence for the treatment of mTLE. Trial registration ClinicalTrials.gov NCT03941613. Registered on May 8, 2019. The STARTS protocol has been registered on the US National Institutes of Health. The status of the STARTS was recruiting and the estimated study completion date was December 31, 2021.

Download Full-text