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Timecourse of epileptogenesis in an TSC1 inducible mouse model

ABSTRACT: To determine how the loss of TSC induces epileptogenesis, we made use of an inducible Tsc1 knock-out mouse model. Tsc1 was homozygously deleted in all CAMK2A positive neurons. Hippocampal tissue was collected at different time points after gene deletion and during epileptogenesis, of mice of both sexes. Also, mice treated with 10mg/kg rapamycin were included in the experiment. Using RNA-seq analysis, we identified differentially expressed genes encoding either ion channel and/or genes belonging to the GO-term ‘action potential’. Of these genes, 50% were already significantly dysregulated before or just around seizure onset, suggesting that these genes could be driver genes of epileptogenesis. Of the genes encoding ion channels or belonging to the Gene Ontology term action potential, 27 were differentially expressed just before seizure onset, suggesting a potential driving role in epileptogenesis. Our data highlight the complex changes driving epileptogenesis in TSC, including the changed expression of multiple ion channels. Our study emphasizes inhibition of the TSC/mTOR signaling pathway as a promising therapeutic approach to target epilepsy in patients with TSC.

ORGANISM(S): Mus musculus

PROVIDER: GSE164306 | GEO | 2021/11/11

REPOSITORIES: GEO

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