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Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

ABSTRACT: Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

PROVIDER: PRJNA663025 | ENA |

REPOSITORIES: ENA

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Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

Project description:A novel model of drug-resistant epilepsy based on the selection of mice treated with phenytoin (PHT) in the 6 Hz seizure model was developed. It leads to the identification of subpopulations of drug-responder and non-responder mice. Transcriptional characterization of the hippocampi from these 2 sub-populations was performed and compared. No significant difference has been observed between the 2 sample groups.

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Circulating MicroRNAs From Serum Small Extracellular Vesicles as Potential diagnostic Biomarkers in Pediatric Epilepsy and Drug-Resistant Epilepsy

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Project description:Changes in calcium homeostasis and gene expression implicated in epilepsy in hippocampi of mice overexpressing ORAI1

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Identification of gene regulatory networks affected across drug-resistant epilepsies

Project description: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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