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...

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Main Authors: Yue Li, S Thameem Dheen, Fengru Tang, Yumin Luo, Ran Meng, Tay Sam Wah Samuel, Lan Zhang
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/12/3012
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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.
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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
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