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

Wang, Zhi-Bin; Qu, Jian; Yang, Zhiyong; Liu, Ding-Yang; Jiang, Shilong; Zhang, Ying; Yang, Zhiquan; Mao, Xiao‐Yuan; Liu, Zhao‐Qian

doi:10.3389/fnins.2022.892022

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…To our knowledge, available transcriptomics datasets for epilepsy are often limited to one pathology, lacking comparison across epilepsies, and are low in sample number [11][12][13][14][15] . Therefore, further investigation of a larger cohort involving different pathologies can extend our understanding of the pathobiological mechanisms that underly epilepsy.…”

Section: Introductionmentioning

confidence: 99%

Identification of gene regulatory networks affected across drug-resistant epilepsies

Aronica

Romagnolo

Anink

et al. 2023

Preprint

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Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study is the first to apply a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify novel therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering novel opportunities for drug-target discovery and development.

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Section: Introductionmentioning

confidence: 99%

Identification of gene regulatory networks affected across drug-resistant epilepsies

Aronica

Romagnolo

Anink

et al. 2023

Preprint

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Identification of gene regulatory networks affected across drug-resistant epilepsies

François,

Romagnolo,

Luinenburg

et al. 2024

Nat Commun

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Epilepsy is a chronic and heterogenous disease characterized by recurrent unprovoked seizures, that are commonly resistant to antiseizure medications. This study applies a transcriptome network-based approach across epilepsies aiming to improve understanding of molecular disease pathobiology, recognize affected biological mechanisms and apply causal reasoning to identify therapeutic hypotheses. This study included the most common drug-resistant epilepsies (DREs), such as temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and mTOR pathway-related malformations of cortical development (mTORopathies). This systematic comparison characterized the global molecular signature of epilepsies, elucidating the key underlying mechanisms of disease pathology including neurotransmission and synaptic plasticity, brain extracellular matrix and energy metabolism. In addition, specific dysregulations in neuroinflammation and oligodendrocyte function were observed in TLE-HS and mTORopathies, respectively. The aforementioned mechanisms are proposed as molecular hallmarks of DRE with the identified upstream regulators offering opportunities for drug-target discovery and development.

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Single-cell sequencing combined with machine learning reveals the mechanism of interaction between epilepsy and stress cardiomyopathy

Pei²,

Zhang³

et al. 2023

Front. Immunol.

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BackgroundEpilepsy is a disorder that can manifest as abnormalities in neurological or physical function. Stress cardiomyopathy is closely associated with neurological stimulation. However, the mechanisms underlying the interrelationship between epilepsy and stress cardiomyopathy are unclear. This paper aims to explore the genetic features and potential molecular mechanisms shared in epilepsy and stress cardiomyopathy.MethodsBy analyzing the epilepsy dataset and stress cardiomyopathy dataset separately, the intersection of the two disease co-expressed differential genes is obtained, the co-expressed differential genes reveal the biological functions, the network is constructed, and the core modules are identified to reveal the interaction mechanism, the co-expressed genes with diagnostic validity are screened by machine learning algorithms, and the co-expressed genes are validated in parallel on the epilepsy single-cell data and the stress cardiomyopathy rat model.ResultsEpilepsy causes stress cardiomyopathy, and its key pathways are Complement and coagulation cascades, HIF-1 signaling pathway, its key co-expressed genes include SPOCK2, CTSZ, HLA-DMB, ALDOA, SFRP1, ERBB3. The key immune cell subpopulations localized by single-cell data are the T_cells subgroup, Microglia subgroup, Macrophage subgroup, Astrocyte subgroup, and Oligodendrocytes subgroup.ConclusionWe believe epilepsy causing stress cardiomyopathy results from a multi-gene, multi-pathway combination. We identified the core co-expressed genes (SPOCK2, CTSZ, HLA-DMB, ALDOA, SFRP1, ERBB3) and the pathways that function in them (Complement and coagulation cascades, HIF-1 signaling pathway, JAK-STAT signaling pathway), and finally localized their key cellular subgroups (T_cells subgroup, Microglia subgroup, Macrophage subgroup, Astrocyte subgroup, and Oligodendrocytes subgroup). Also, combining cell subpopulations with hypercoagulability as well as sympathetic excitation further narrowed the cell subpopulations of related functions.

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

Cited by 3 publications

References 52 publications

Identification of gene regulatory networks affected across drug-resistant epilepsies

Identification of gene regulatory networks affected across drug-resistant epilepsies

Identification of gene regulatory networks affected across drug-resistant epilepsies

Single-cell sequencing combined with machine learning reveals the mechanism of interaction between epilepsy and stress cardiomyopathy

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