Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims
The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA sequencing in postmortem DMPFC samples to investigate suicide victims compar...
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| Format: | Article |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7067 |
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| author | Fanni Dóra Éva Renner Dávid Keller Miklós Palkovits Árpád Dobolyi |
| author_facet | Fanni Dóra Éva Renner Dávid Keller Miklós Palkovits Árpád Dobolyi |
| author_sort | Fanni Dóra |
| collection | DOAJ |
| description | The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. 1400 genes differed using log2FC > ±1 and adjusted <i>p</i>-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Protein–protein interaction and co-expressional networks coupled with gene set enrichment analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated, while glutamatergic synaptic signaling upregulated genes in suicidal individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding protein 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in two different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims. |
| first_indexed | 2024-03-09T21:50:50Z |
| format | Article |
| id | doaj.art-5900c3997e9d4f34b543a9124076c582 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:50:50Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5900c3997e9d4f34b543a9124076c5822023-11-23T20:07:21ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313706710.3390/ijms23137067Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide VictimsFanni Dóra0Éva Renner1Dávid Keller2Miklós Palkovits3Árpád Dobolyi4Human Brain Tissue Bank, Semmelweis University, 1094 Budapest, HungaryHuman Brain Tissue Bank, Semmelweis University, 1094 Budapest, HungaryLaboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, 1094 Budapest, HungaryHuman Brain Tissue Bank, Semmelweis University, 1094 Budapest, HungaryLaboratory of Neuromorphology, Department of Anatomy, Histology and Embryology, Semmelweis University, 1094 Budapest, HungaryThe default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. 1400 genes differed using log2FC > ±1 and adjusted <i>p</i>-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Protein–protein interaction and co-expressional networks coupled with gene set enrichment analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated, while glutamatergic synaptic signaling upregulated genes in suicidal individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding protein 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in two different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.https://www.mdpi.com/1422-0067/23/13/7067depressionprefrontal cortexRNA sequencingbioinformaticsgene set enrichmentprotein–protein interaction network |
| spellingShingle | Fanni Dóra Éva Renner Dávid Keller Miklós Palkovits Árpád Dobolyi Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims International Journal of Molecular Sciences depression prefrontal cortex RNA sequencing bioinformatics gene set enrichment protein–protein interaction network |
| title | Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims |
| title_full | Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims |
| title_fullStr | Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims |
| title_full_unstemmed | Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims |
| title_short | Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims |
| title_sort | transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims |
| topic | depression prefrontal cortex RNA sequencing bioinformatics gene set enrichment protein–protein interaction network |
| url | https://www.mdpi.com/1422-0067/23/13/7067 |
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