Abstract
Seizure clustering is a common phenomenon in epilepsy. Protein expression profiles during a seizure cluster might reflect the pathomechanism underlying ictogenesis. We performed proteomic analyses to identify proteins with a specific temporal expression pattern in cluster phases and to demonstrate their potential pathomechanistic role. Pilocarpine epilepsy model mice with confirmed cluster pattern of spontaneous recurrent seizures by long-term video-electroencpehalography were sacrificed at the onset, peak, or end of a seizure cluster or in the seizure-free period. Proteomic analysis was performed in the hippocampus and the cortex. Differentially expressed proteins (DEPs) were identified and classified according to their temporal expression pattern. Among the five hippocampal (HC)-DEP classes, HC-class 1 (66 DEPs) represented disrupted cell homeostasis due to clustered seizures, HC-class 2 (63 DEPs) cluster-onset downregulated processes, HC-class 3 (42 DEPs) cluster-onset upregulated processes, and HC-class 4 (103 DEPs) consequences of clustered seizures. Especially, DEPs in HC-class 3 were hippocampus-specific and involved in axonogenesis, synaptic vesicle assembly, and neuronal projection, indicating their pathomechanistic roles in ictogenesis. Key proteins in HC-class 3 were highly interconnected and abundantly involved in those biological processes. This study described the seizure cluster-associated spatiotemporal regulation of protein expression. HC-class 3 provides insights regarding ictogenesis-related processes.
Highlights
Complex regulatory networks among mRNAs, micro RNAs, long non-coding RNAs, circular RNAs, and proteins in epilepsy pathogenesis have been increasingly elucidated, based on genomic, epigenomic, and proteomic analyses[8,9,10,11,12,13,14]
12 mice in total were selected for the proteomic analysis
This study performed a proteomic analysis in the hippocampus of a murine pilocarpine-induced chronic epilepsy model and demonstrated classes of differentially expressed proteins with distinct expression patterns during a seizure cluster, as well as their pathogenetic functions and involved biological processes
Summary
Complex regulatory networks among mRNAs, micro RNAs, long non-coding RNAs, circular RNAs, and proteins in epilepsy pathogenesis have been increasingly elucidated, based on genomic, epigenomic, and proteomic analyses[8,9,10,11,12,13,14]. Given that the dynamic changes in those regulatory networks might be fundamentally involved in the periodic occurrence of seizure clusters, proteomic analysis has the advantage that it addresses the most downstream target of those regulatory networks. This enables the evaluation of highly dynamic and locationspecific cellular processes and reflects comprehensively the effects of those complex regulatory networks[15]. To identify proteins with a specific temporal expression pattern during a seizure cluster and to demonstrate their potential pathomechanistic roles, we performed brain proteomic analyses in a murine pilocarpine epilepsy model
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