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Single-nucleus RNA sequencing-based construction of a hippocampal neuron atlas in mice with epileptic memory impairment

ABSTRACT: In this study, we utilized snRNA-seq to explore the transcriptional changes in hippocampal neurons of drug-resistant mice with memory disorder in epilepsy, and analyzed the inter-group heterogeneity of 20 subclasses of neurons, focusing on aspects such as cell communication, gene expressions, GO and KEGG enrichment analysis, and module gene set analysis. Our data provides a comprehensive transcriptomic description of the neuronal population affected by drug-resistant epileptic memory disorders. Further studies have shown that specific neuronal subpopulations impact synaptic plasticity through the regulation of relevant target genes by specific transcription factors.

ORGANISM(S): Mus musculus

PROVIDER: GSE241349 | GEO | 2024/12/18

REPOSITORIES: GEO

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Project description:<h4><strong>INTRODUCTION: </strong>Approximately 1% of the world's population is impacted by epilepsy, a chronic neurological disorder characterized by seizures. One-third of epileptic patients are resistant to AEDs, or have medically refractory epilepsy (MRE). One non-invasive treatment that exists for MRE includes the ketogenic diet, a high-fat, low-carbohydrate diet. Despite the KD's success in seizure attenuation, it has a few risks and its mechanisms remain poorly understood. The KD has been shown to improve metabolism and mitochondrial function in epileptic phenotypes. Potassium channels have implications in epileptic conditions as they have dual roles as metabolic sensors and control neuronal excitation.</h4><h4><strong>OBJECTIVES: </strong>The goal of this study was to explore changes in the lipidome in hippocampal and cortical tissue from Kv1.1-KO model of epilepsy.</h4><h4><strong>METHODS: </strong>FT-ICR/MS analysis was utilized to examine nonpolar metabolome of cortical and hippocampal tissue isolated from a Kv1.1 channel knockout mouse model of epilepsy (n = 5) and wild-type mice (n = 5).</h4><h4><strong>RESULTS: </strong>Distinct metabolic profiles were observed, significant (p < 0.05) features in hippocampus often being upregulated (FC ≥ 2) and the cortex being downregulated (FC ≤ 0.5). Pathway enrichment analysis shows lipid biosynthesis was affected. Partition ratio analysis revealed that the ratio of most metabolites tended to be increased in Kv1.1-/-. Metabolites in hippocampal tissue were commonly upregulated, suggesting seizure initiation in the hippocampus. Aberrant mitochondrial function is implicated by the upregulation of cardiolipin, a common component in the mitochondrial membrane.</h4><h4><strong>CONCLUSION: </strong>Generally, our study finds that the lipidome is changed in the hippocampus and cortex in response to Kv1.1-KO indicating changes in membrane structural integrity and synaptic transmission.</h4>

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Single-nucleus RNA sequencing-based construction of a hippocampal neuron atlas in mice with epileptic memory impairment

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