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Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy

ABSTRACT: Lipid-accumulated reactive astrocytes promote seizure activity in epilepsy

PROVIDER: PRJNA787216 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17168016_1.fastq.gz	Fastqsanger.gz
	SRR17168016_2.fastq.gz	Fastqsanger.gz
	SRR17168017_1.fastq.gz	Fastqsanger.gz
	SRR17168017_2.fastq.gz	Fastqsanger.gz
	SRR17168018_1.fastq.gz	Fastqsanger.gz

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

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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 [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 disease progression in epilepsy (Human lipidomics)

Project description:Reactive astrocytes play an important role in neurological diseases, but their molecular and functional phenotypes in epilepsy are unclear. Here, we show that in patients with temporal lobe epilepsy (TLE) and mouse models of epilepsy, excessive lipid accumulation in astrocytes leads to the formation of lipid-accumulated reactive astrocytes (LARAs), a new reactive astrocyte subtype characterized by elevated APOE expression. Genetic knockout of APOE inhibited LARA formation and seizure activities in epileptic mice. Single-nucleus RNA sequencing in TLE patients confirmed the existence of a LARA subpopulation with a distinct molecular signature. Functional studies in epilepsy mouse models and human brain slices showed that LARAs promote neuronal hyperactivity and disease progression. Targeting LARAs by intervention with lipid transport and metabolism could thus provide new therapeutic options for drug-resistant TLE. Human lipidomics is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS8856' rel='noopener noreferrer' target='_blank'>MTBLS8856</a>.Mice lipidomics reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS8865' rel='noopener noreferrer' target='_blank'>MTBLS8865</a>.

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Lipid-accumulated reactive astrocytes promote disease progression in epilepsy (Mice lipidomics)

Project description:Reactive astrocytes play an important role in neurological diseases, but their molecular and functional phenotypes in epilepsy are unclear. Here, we show that in patients with temporal lobe epilepsy (TLE) and mouse models of epilepsy, excessive lipid accumulation in astrocytes leads to the formation of lipid-accumulated reactive astrocytes (LARAs), a new reactive astrocyte subtype characterized by elevated APOE expression. Genetic knockout of APOE inhibited LARA formation and seizure activities in epileptic mice. Single-nucleus RNA sequencing in TLE patients confirmed the existence of a LARA subpopulation with a distinct molecular signature. Functional studies in epilepsy mouse models and human brain slices showed that LARAs promote neuronal hyperactivity and disease progression. Targeting LARAs by intervention with lipid transport and metabolism could thus provide new therapeutic options for drug-resistant TLE. Mice lipidomics is reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS8865' rel='noopener noreferrer' target='_blank'>MTBLS8865</a>.Human lipidomics reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS8856' rel='noopener noreferrer' target='_blank'>MTBLS8856</a>.

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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 [Human bulk RNA-seq]

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