| Summary: | An epileptic seizure generates massive neuronal activity in the brain which induces de novo transcription and translation, bringing about cellular changes which may contribute to epileptogenesis. To understand the cell-type-specific molecular changes brought about by seizures, I isolated nuclei from forebrain excitatory neurons of a pilocarpine-induced transgenic mouse and profiled the nuclear transcriptome and proteome. My nuclear transcriptome analyses show that expression of genes related to MAPK signalling are upregulated while a major class of C2H2-type zinc finger proteins, including those containing KRAB domains, are downregulated in seizure-induced animals. In parallel, nuclear proteome analyses uncovered AP-1 complex components and post-translational modifications such as SUMOylation and ubiquitin-like conjugation to be enriched in the seizure group. Finally, I show that changes in nuclear TEF levels are activity-dependent in forebrain excitatory neurons of seizure-induced mice, as well as in cultured hippocampal neurons after stimulation with convulsant drugs. These findings further our understanding of seizure-induced nuclear events in neurons which are relevant to epileptogenesis. My study also demonstrates a robust nuclear profiling method amenable to different sequencing platforms for other cell types.
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