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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE190453 | GEO | 2023/02/08

REPOSITORIES: GEO

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

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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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [single-cell RNA-seq]

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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [Human bulk RNA-seq]

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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy

Project description:Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy

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

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

| PRJNA808397 | ENA

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

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

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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [single-cell RNA-seq]

Project description:Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [single-cell RNA-seq]

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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [Human bulk RNA-seq]

Project description:Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy [Human bulk RNA-seq]

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Reactive astrocytes secrete lcn2 to promote neuron death.

Project description:Glial reaction is a common feature of neurodegenerative diseases. Recent studies have suggested that reactive astrocytes gain neurotoxic properties, but exactly how reactive astrocytes contribute to neurotoxicity remains to be determined. Here, we identify lipocalin 2 (lcn2) as an inducible factor that is secreted by reactive astrocytes and that is selectively toxic to neurons. We show that lcn2 is induced in reactive astrocytes in transgenic rats with neuronal expression of mutant human TAR DNA-binding protein 43 (TDP-43) or RNA-binding protein fused in sarcoma (FUS). Therefore, lcn2 is induced in activated astrocytes in response to neurodegeneration, but its induction is independent of TDP-43 or FUS expression in astrocytes. We found that synthetic lcn2 is cytotoxic to primary neurons in a dose-dependent manner, but is innocuous to astrocytes, microglia, and oligodendrocytes. Lcn2 toxicity is increased in neurons that express a disease gene, such as mutant FUS or TDP-43. Conditioned medium from rat brain slice cultures with neuronal expression of mutant TDP-43 contains abundant lcn2 and is toxic to primary neurons as well as neurons in cultured brain slice from WT rats. Partial depletion of lcn2 by immunoprecipitation reduced conditioned medium-mediated neurotoxicity. Our data indicate that reactive astrocytes secrete lcn2, which is a potent neurotoxic mediator.

| S-EPMC3593910 | biostudies-literature

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