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.