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

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 epilep...

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Autores principales: Li, Xiang, Wang, Qing, Zhang, Dian-wen, Wu, Di, Zhang, Si-wei, Wei, Zheng-ren, Chen, Xia, Li, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957222/
https://www.ncbi.nlm.nih.gov/pubmed/35345815
http://dx.doi.org/10.3389/fphar.2022.820508
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author Li, Xiang
Wang, Qing
Zhang, Dian-wen
Wu, Di
Zhang, Si-wei
Wei, Zheng-ren
Chen, Xia
Li, Wei
author_facet Li, Xiang
Wang, Qing
Zhang, Dian-wen
Wu, Di
Zhang, Si-wei
Wei, Zheng-ren
Chen, Xia
Li, Wei
author_sort Li, Xiang
collection PubMed
description 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.
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spelling pubmed-89572222022-03-27 Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808 Li, Xiang Wang, Qing Zhang, Dian-wen Wu, Di Zhang, Si-wei Wei, Zheng-ren Chen, Xia Li, Wei Front Pharmacol Pharmacology 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. Frontiers Media S.A. 2022-03-08 /pmc/articles/PMC8957222/ /pubmed/35345815 http://dx.doi.org/10.3389/fphar.2022.820508 Text en Copyright © 2022 Li, Wang, Zhang, Wu, Zhang, Wei, Chen and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Xiang
Wang, Qing
Zhang, Dian-wen
Wu, Di
Zhang, Si-wei
Wei, Zheng-ren
Chen, Xia
Li, Wei
Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808
title Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808
title_full Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808
title_fullStr Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808
title_full_unstemmed Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808
title_short Hippocampus RNA Sequencing of Pentylenetetrazole-Kindled Rats and Upon Treatment of Novel Chemical Q808
title_sort hippocampus rna sequencing of pentylenetetrazole-kindled rats and upon treatment of novel chemical q808
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8957222/
https://www.ncbi.nlm.nih.gov/pubmed/35345815
http://dx.doi.org/10.3389/fphar.2022.820508
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