Temporal changes in mouse hippocampus transcriptome after pilocarpine-induced seizures

作者：Evgenya Y. Popova, Yuka Imamura Kawasawa, Ming Leung, Colin J. Barnstable · 发表于：Frontiers in Neuroscience · 年份：2024 · DOI：10.3389/fnins.2024.1384805 · 被引用次数：13 · 研究领域：Epilepsy research and treatment、Neurogenesis and neuroplasticity mechanisms、Neuroscience and Neuropharmacology Research

Introduction: Status epilepticus (SE) is a seizure lasting more than 5 min that can have lethal consequences or lead to various neurological disorders, including epilepsy. Using a pilocarpine-induced SE model in mice we investigated temporal changes in the hippocampal transcriptome. Methods: We performed mRNA-seq and microRNA-seq analyses at various times after drug treatment. Results: At 1 h after the start of seizures, hippocampal cells upregulated transcription of immediate early genes and genes involved in the IGF-1, ERK/MAPK and RNA-PolII/transcription pathways. At 8 h, we observed changes in the expression of genes associated with oxidative stress, overall transcription downregulation, particularly for genes related to mitochondrial structure and function, initiation of a stress response through regulation of ribosome and translation/EIF2 signaling, and upregulation of an inflammatory response. During the middle of the latent period, 36 h, we identified upregulation of membrane components, cholesterol synthesis enzymes, channels, and extracellular matrix (ECM), as well as an increased inflammatory response. At the end of the latent period, 120 h, most changes in expression were in genes involved in ion transport, membrane channels, and synapses. Notably, we also elucidated the involvement of novel pathways, such as cholesterol biosynthesis pathways, iron/BMP/ferroptosis pathways, and circadian rhythms signaling in SE and epileptogenesis. Discussion: These temporal chang...