Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus
Objective: To investigate microRNA (miRNA) expression profiles before and after pilocarpine-induced status epilepticus (SE) in the cornu ammonis (CA) and dentated gyrus (DG) areas of the mouse hippocampus, and to predict the downstream proteins and related pathways based on bioinformatic analysis. M...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-11-01
|
Series: | Biomedicines |
Subjects: | |
Online Access: | https://www.mdpi.com/2227-9059/10/12/3012 |
_version_ | 1797461341343055872 |
---|---|
author | Yue Li S Thameem Dheen Fengru Tang Yumin Luo Ran Meng Tay Sam Wah Samuel Lan Zhang |
author_facet | Yue Li S Thameem Dheen Fengru Tang Yumin Luo Ran Meng Tay Sam Wah Samuel Lan Zhang |
author_sort | Yue Li |
collection | DOAJ |
description | Objective: To investigate microRNA (miRNA) expression profiles before and after pilocarpine-induced status epilepticus (SE) in the cornu ammonis (CA) and dentated gyrus (DG) areas of the mouse hippocampus, and to predict the downstream proteins and related pathways based on bioinformatic analysis. Methods: An epileptic mouse model was established using a pilocarpine injection. Brain tissues from the CA and DG were collected separately for miRNA analysis. The miRNAs were extracted using a kit, and the expression profiles were generated using the SurePrint G3 Mouse miRNA microarray and validated. The intersecting genes of TargetScan and miRanda were selected to predict the target genes of each miRNA. For gene ontology (GO) studies, the parent-child-intersection (pci) method was used for enrichment analysis, and Benjamini-Hochberg was used for multiple test correction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to detect disease-related pathways among the large list of miRNA-targeted genes. All analyses mentioned above were performed at the time points of control, days 3, 14, and 60 post-SE. Results: Control versus days 3, 14, and 60 post-SE: in the CA area, a total of 131 miRNAs were differentially expressed; 53, 49, and 26 miRNAs were upregulated and 54, 10, and 22 were downregulated, respectively. In the DG area, a total of 171 miRNAs were differentially expressed; furthermore, 36, 32, and 28 miRNAs were upregulated and 78, 58, and 44 were downregulated, respectively. Of these, 92 changed in both the CA and DG, 39 only in the CA, and 79 only in the DG area. The differentially expressed miRNAs target 11–1630 genes. Most of these proteins have multiple functions in epileptogenesis. There were 15 common pathways related to altered miRNAs: nine different pathways in the CA and seven in the DG area. Conclusions: Stage- and subfield-associated hippocampal miRNA expression patterns are closely related to epileptogenesis, although the detailed mechanisms need to be explored in the future. |
first_indexed | 2024-03-09T17:18:02Z |
format | Article |
id | doaj.art-3b7668ba6269420eabe99bd7f3a56758 |
institution | Directory Open Access Journal |
issn | 2227-9059 |
language | English |
last_indexed | 2024-03-09T17:18:02Z |
publishDate | 2022-11-01 |
publisher | MDPI AG |
record_format | Article |
series | Biomedicines |
spelling | doaj.art-3b7668ba6269420eabe99bd7f3a567582023-11-24T13:25:10ZengMDPI AGBiomedicines2227-90592022-11-011012301210.3390/biomedicines10123012Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status EpilepticusYue Li0S Thameem Dheen1Fengru Tang2Yumin Luo3Ran Meng4Tay Sam Wah Samuel5Lan Zhang6Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeDepartment of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeRadiation Physiology Lab, Singapore Nuclear Research and Safety Initiative, National University of Singapore, Singapore 138602, SingaporeDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, ChinaDepartment of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, ChinaDepartment of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, SingaporeDepartment of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing 100053, ChinaObjective: To investigate microRNA (miRNA) expression profiles before and after pilocarpine-induced status epilepticus (SE) in the cornu ammonis (CA) and dentated gyrus (DG) areas of the mouse hippocampus, and to predict the downstream proteins and related pathways based on bioinformatic analysis. Methods: An epileptic mouse model was established using a pilocarpine injection. Brain tissues from the CA and DG were collected separately for miRNA analysis. The miRNAs were extracted using a kit, and the expression profiles were generated using the SurePrint G3 Mouse miRNA microarray and validated. The intersecting genes of TargetScan and miRanda were selected to predict the target genes of each miRNA. For gene ontology (GO) studies, the parent-child-intersection (pci) method was used for enrichment analysis, and Benjamini-Hochberg was used for multiple test correction. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to detect disease-related pathways among the large list of miRNA-targeted genes. All analyses mentioned above were performed at the time points of control, days 3, 14, and 60 post-SE. Results: Control versus days 3, 14, and 60 post-SE: in the CA area, a total of 131 miRNAs were differentially expressed; 53, 49, and 26 miRNAs were upregulated and 54, 10, and 22 were downregulated, respectively. In the DG area, a total of 171 miRNAs were differentially expressed; furthermore, 36, 32, and 28 miRNAs were upregulated and 78, 58, and 44 were downregulated, respectively. Of these, 92 changed in both the CA and DG, 39 only in the CA, and 79 only in the DG area. The differentially expressed miRNAs target 11–1630 genes. Most of these proteins have multiple functions in epileptogenesis. There were 15 common pathways related to altered miRNAs: nine different pathways in the CA and seven in the DG area. Conclusions: Stage- and subfield-associated hippocampal miRNA expression patterns are closely related to epileptogenesis, although the detailed mechanisms need to be explored in the future.https://www.mdpi.com/2227-9059/10/12/3012epilepsycornu ammonisdentate gyrusmiRNA expression pattern |
spellingShingle | Yue Li S Thameem Dheen Fengru Tang Yumin Luo Ran Meng Tay Sam Wah Samuel Lan Zhang Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus Biomedicines epilepsy cornu ammonis dentate gyrus miRNA expression pattern |
title | Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus |
title_full | Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus |
title_fullStr | Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus |
title_full_unstemmed | Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus |
title_short | Stage- and Subfield-Associated Hippocampal miRNA Expression Patterns after Pilocarpine-Induced Status Epilepticus |
title_sort | stage and subfield associated hippocampal mirna expression patterns after pilocarpine induced status epilepticus |
topic | epilepsy cornu ammonis dentate gyrus miRNA expression pattern |
url | https://www.mdpi.com/2227-9059/10/12/3012 |
work_keys_str_mv | AT yueli stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus AT sthameemdheen stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus AT fengrutang stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus AT yuminluo stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus AT ranmeng stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus AT taysamwahsamuel stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus AT lanzhang stageandsubfieldassociatedhippocampalmirnaexpressionpatternsafterpilocarpineinducedstatusepilepticus |