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Vahid Mansouri1 
, Babak Arjmand2 , Nastaran Asri3 , Zahra Razzaghi4 , Mostafa Rezaei-Tavirani * 1, Farideh Razi5 , Fatemeh Bandarian6 , Reza M Robati7 , Mitra Rezaei8
, Babak Arjmand2 , Nastaran Asri3 , Zahra Razzaghi4 , Mostafa Rezaei-Tavirani * 1, Farideh Razi5 , Fatemeh Bandarian6 , Reza M Robati7 , Mitra Rezaei8
1- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
3- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Disease, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
6- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
7- Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
8- Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
2- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
3- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Disease, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4- Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
6- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
7- Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
8- Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Background: Sleep is an essential process for restoring brain function and is recognized as a fundamental aspect of physical and mental health. The aim of this study is to assess the molecular mechanisms of insomnia disorder and to identify the key dysregulated genes associated with it.
Methods: To study molecular mechanisms of insomnia, GSE208668 was selected from the Gene Expression Omnibus (GEO) database. Total RNA from peripheral blood mononuclear cells (PBMCs) of 17 individuals with insomnia disorder was analyzed and compared to 25 controls using the GEO2R program. The gene expression profiles were assessed using box plot, Uniform Manifold Approximation and Projection (UMAP) plot, expression density diagram, and Venn diagram. The significant differentially expressed genes (DEGs) were evaluated through a directed protein-protein interaction (PPI) network using the CluePedia plugin of Cytoscape software, considering co-expression interactions. The central nodes were identified as the most influential and regulated genes.
Results: Pre-evaluation analysis revealed that insomnia exhibits heterogeneity and can be divided into two groups. The gene expression profiles of the first group were similar to those of the insomnia group, while the second group of controls was distinguished from the insomnia group by genes such as TP53, CCND1, IL1B, SOX1, and NOTCH1, which were identified as key actor genes. Additionally, IL10, IL6, TP53, PTGS2, ESR1, PTEN, JUN, CREB1, CDKN1ACDKN2A, CXCR4, and GATA3 were identified as important regulatory genes.
Conclusion: It can be concluded that many individuals may be potentially involved in insomnia disorder as pre-insomnia. The findings demonstrate that pre-insomnia and insomnia share very similar molecular mechanisms. The critical genes TP53, CCND1, IL1B, SOX1, and NOTCH1, along with pathways related to apoptosis, inflammation, immunological response, and changes in sleep quality, are emphasized as particularly relevant to insomnia disorder.
Methods: To study molecular mechanisms of insomnia, GSE208668 was selected from the Gene Expression Omnibus (GEO) database. Total RNA from peripheral blood mononuclear cells (PBMCs) of 17 individuals with insomnia disorder was analyzed and compared to 25 controls using the GEO2R program. The gene expression profiles were assessed using box plot, Uniform Manifold Approximation and Projection (UMAP) plot, expression density diagram, and Venn diagram. The significant differentially expressed genes (DEGs) were evaluated through a directed protein-protein interaction (PPI) network using the CluePedia plugin of Cytoscape software, considering co-expression interactions. The central nodes were identified as the most influential and regulated genes.
Results: Pre-evaluation analysis revealed that insomnia exhibits heterogeneity and can be divided into two groups. The gene expression profiles of the first group were similar to those of the insomnia group, while the second group of controls was distinguished from the insomnia group by genes such as TP53, CCND1, IL1B, SOX1, and NOTCH1, which were identified as key actor genes. Additionally, IL10, IL6, TP53, PTGS2, ESR1, PTEN, JUN, CREB1, CDKN1ACDKN2A, CXCR4, and GATA3 were identified as important regulatory genes.
Conclusion: It can be concluded that many individuals may be potentially involved in insomnia disorder as pre-insomnia. The findings demonstrate that pre-insomnia and insomnia share very similar molecular mechanisms. The critical genes TP53, CCND1, IL1B, SOX1, and NOTCH1, along with pathways related to apoptosis, inflammation, immunological response, and changes in sleep quality, are emphasized as particularly relevant to insomnia disorder.
Type of Study: Original |
Subject:
Behavioral Neuroscience
Received: 2024/12/14 | Accepted: 2025/01/7
Received: 2024/12/14 | Accepted: 2025/01/7
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