Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808

Abstract

The expression of genes altered in epilepsy remains incomplete, particularly in the hippocampus, which exhibits exquisite vulnerability to epilepsy. Q808 is an innovation chemical compound that has potent anti-convulsant effect. Exploring its mechanism can not only explore the pathogenesis of epilepsy but also provide a theoretical basis for its clinical application. The present study aimed to use RNA sequencing (RNA-seq) to reveal the gene transcriptomic profile of chronic pentylenetetrazole (PTZ)-kindled seizure rats and the difference of the PTZ model rat before and after treatment with Q808. Quantitative real-time PCR (qRT-PCR) was performed to validate the RNA-seq results. The protein level was estimated with Western blot. Hippocampal transcriptomic analysis showed that 289 differentially expressed genes (DEGs) were confirmed in the PTZ-kindled seizure group compared with the vehicle control. Gene cluster analysis identified most of the DEGs linked to neuronal apoptosis, neurogenesis, neuronal projections, and neurotransmitter regulation. After analysis across the three groups, 23 hub genes and 21 pathways were identified, and qRT-PCR analysis confirmed that most of the mRNA levels of hub genes were consistent with the RNA-seq results. Q808 treatment increased the level of ACE, a GABA-related protein. Our analysis showed the comprehensive compendium of genes and pathways differentially expressed for PTZ-kindled seizure rats and upon Q808 treatment in PTZ-kindled seizure, which may provide a theoretical basis to explore the mechanism and unique efficacy of Q808 and the pathophysiology of epilepsy in the future.

RNA Sequencing Demonstrates Ex Vivo Neocortical Transcriptomic Changes Induced by Epileptiform Activity in Male and Female Mice

“…Many groups have demonstrated large-scale transcriptomic changes during seizure activity ( Okamoto et al, 2010 ; Hawkins and Kearney, 2012 ; Dixit et al, 2016 ; Guelfi et al, 2019 ; O'Leary et al, 2020 ; Li et al, 2022 ), indicating what might be termed the “molecular hallmark” of epileptiform activity. These studies have mainly been conducted using in vivo animal models or postmortem human brain tissue, primarily from hippocampal or whole-brain tissue sections ( Jamali et al, 2006 ; Pitkanen et al, 2015 ; L. Zhang et al, 2018 ; Conte et al, 2020 ).…”

RNA sequencing demonstratesex vivoneocortical transcriptomic changes induced by epileptiform activity in male and female mice

“…Many groups have demonstrated large-scale transcriptomic changes during seizure activity (Dixit et al, 2016; Guelfi et al, 2019; Hawkins & Kearney, 2012; Li et al, 2022; O’Leary et al, 2020; Okamoto et al, 2010), indicating what might be termed the “molecular hallmark” of epileptiform activity. These studies have mainly been conducted using in vivo animal models or postmortem human brain tissue, primarily from hippocampal or whole-brain tissue sections (Conte et al, 2020; Jamali et al, 2006; Pitkanen et al, 2015; Zhang et al, 2018).…”