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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [mouse]

ABSTRACT: Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype

ORGANISM(S): Mus musculus

PROVIDER: GSE197015 | GEO | 2023/02/08

REPOSITORIES: GEO

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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [KA and APOE]

Project description:Abnormal lipid accumulation have been reported in patients with temporal lobe epilepsy (TLE) by in vivo magnetic resonance imaging (MRI). However, the role of astrocytes in the regulation of neuronal activity or lipid metabolism in epilepsy is unclear. Using single-nucleus RNA sequencing of TLE patient samples, we found lipid accumulation and lipid metabolism dysfunction mainly take place in astrocytes. Mechanistic studies revealed that apolipoprotein E (APOE) mediates lipid transfer from hyperactive neurons to astrocytes, turning them into the neurotoxic reactive phenotype

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Leukocyte gene expression predicts human temporal lobe epilepsy seizure frequency

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chronic temporal lobe epilepsy: biopsy hippocampus

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Project description:MicroRNAs (miRNAs) are short noncoding RNAs that shape the gene expression landscape, including during the pathogenesis of temporal lobe epilepsy (TLE). In order to provide a full catalog of the miRNA changes that happen during experimental TLE, we sequenced Argonaute 2-loaded miRNAs in the hippocampus of three different animal models at regular intervals between the time of the initial precipitating insult to the establishment of spontaneous recurrent seizures. The commonly upregulated miRNAs were selected for a functional in vivo screen using oligonucleotide inhibitors. This revealed anti-seizure phenotypes upon inhibition of miR-10a-5p, miR-21-5p and miR-142-5p as well as neuroprotection-only effects for inhibition of miR-27a-3p and miR-431-5p. Pathway enrichment analysis on predicted and validated targets of these miRNAs indicated a role for TGFβ signaling in a shared seizure-modifying mechanism. Together, these results identify functional miRNAs in the hippocampus and a pipeline of new targets for seizure control in epilepsy.

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Project description:Over the past decades, the immune responses have been suspected of participating in the mechanisms for epilepsy. To assess the immune related pathway in temporal lobe epilepsy (TLE), we explored the altered immune pathways in TLE patients with and without hippocampal sclerosis (HS).We analyzed RNA-seq data from 3 TLE-HS and 3 TLE-nonHS patients, including identification of differentially expressed RNA, function pathway enrichment, the protein-protein interaction network and construction of ceRNA regulatory. network. We illustrated the immune related landscape of molecules and pathways on human TLE-HS. Also, we identified several differential immune related genes like HSP90AA1 and SOD1 in TLE-HS patients. Further ceRNA regulatory network analysis found SOX2-OT connected to miR-671-5p and upregulated the target gene SPP1 in TLE-HS patients. Also, we identified both SOX2-OT and SPP1 were significantly upregulated in five different databases including TLE-HS patients and animal models

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2021-01-18 | PXD023048 | Pride

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