Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain
BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Eco-Vector
2023-03-01
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| Series: | Consortium Psychiatricum |
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| Online Access: | https://consortium-psy.com/jour/article/viewFile/219/pdf |
| _version_ | 1797853354634772480 |
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| author | Tuan Nguyen Olga I. Efimova Artem V. Tokarchuk Anna Yu. Morozova Yana A. Zorkina Denis S. Andreyuk George P. Kostyuk Philipp E. Khaitovich |
| author_facet | Tuan Nguyen Olga I. Efimova Artem V. Tokarchuk Anna Yu. Morozova Yana A. Zorkina Denis S. Andreyuk George P. Kostyuk Philipp E. Khaitovich |
| author_sort | Tuan Nguyen |
| collection | DOAJ |
| description | BACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions.
AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions.
METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold.
RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p 0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p 0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways.
CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research. |
| first_indexed | 2024-04-09T19:49:17Z |
| format | Article |
| id | doaj.art-f5cdee5e20fe4205ad87a90d7213be83 |
| institution | Directory Open Access Journal |
| issn | 2712-7672 2713-2919 |
| language | English |
| last_indexed | 2024-04-09T19:49:17Z |
| publishDate | 2023-03-01 |
| publisher | Eco-Vector |
| record_format | Article |
| series | Consortium Psychiatricum |
| spelling | doaj.art-f5cdee5e20fe4205ad87a90d7213be832023-04-03T12:29:13ZengEco-VectorConsortium Psychiatricum2712-76722713-29192023-03-014151610.17816/CP219104Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia BrainTuan Nguyen0https://orcid.org/0000-0002-1703-0404Olga I. Efimova1https://orcid.org/0000-0003-0842-3203Artem V. Tokarchuk2https://orcid.org/0000-0002-9234-5828Anna Yu. Morozova3https://orcid.org/0000-0002-8681-5299Yana A. Zorkina4https://orcid.org/0000-0003-0247-2717Denis S. Andreyuk5https://orcid.org/0000-0002-3349-5391George P. Kostyuk6https://orcid.org/0000-0002-3073-6305Philipp E. Khaitovich7https://orcid.org/0000-0002-4305-0054V. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and TechnologyV. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and TechnologyV. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and TechnologyV. Serbsky National Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian FederationV. Serbsky National Medical Research Centre of Psychiatry and Narcology of the Ministry of Health of the Russian FederationMental-health Clinic No. 1 named after N.A. AlexeevMental-health Clinic No. 1 named after N.A. AlexeevV. Zelman Center for Neurobiology and Brain Restoration, Skolkovo Institute of Science and TechnologyBACKGROUND: Transcriptomic studies of the brains of schizophrenia (SZ) patients have produced abundant but largely inconsistent findings about the disorders pathophysiology. These inconsistencies might stem not only from the heterogeneous nature of the disorder, but also from the unbalanced focus on particular cortical regions and protein-coding genes. Compared to protein-coding transcripts, long intergenic non-coding RNA (lincRNA) display substantially greater brain region and disease response specificity, positioning them as prospective indicators of SZ-associated alterations. Further, a growing understanding of the systemic character of the disorder calls for a more systematic screening involving multiple diverse brain regions. AIM: We aimed to identify and interpret alterations of the lincRNA expression profiles in SZ by examining the transcriptomes of 35 brain regions. METHODS: We measured the transcriptome of 35 brain regions dissected from eight adult brain specimens, four SZ patients, and four healthy controls, using high-throughput RNA sequencing. Analysis of these data yielded 861 annotated human lincRNAs passing the detection threshold. RESULTS: Of the 861 detected lincRNA, 135 showed significant region-dependent expression alterations in SZ (two-way ANOVA, BH-adjusted p 0.05) and 37 additionally showed significant differential expression between HC and SZ individuals in at least one region (post hoc Tukey test, p 0.05). For these 37 differentially expressed lincRNAs (DELs), 88% of the differences occurred in a cluster of brain regions containing axon-rich brain regions and cerebellum. Functional annotation of the DEL targets further revealed stark enrichment in neurons and synaptic transmission terms and pathways. CONCLUSION: Our study highlights the utility of a systematic brain transcriptome analysis relying on the expression profiles measured across multiple brain regions and singles out white matter regions as a prospective target for further SZ research.https://consortium-psy.com/jour/article/viewFile/219/pdfschizophrenialong intergenic non-coding rnalincrnawhite mattertranscriptomebrain |
| spellingShingle | Tuan Nguyen Olga I. Efimova Artem V. Tokarchuk Anna Yu. Morozova Yana A. Zorkina Denis S. Andreyuk George P. Kostyuk Philipp E. Khaitovich Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain Consortium Psychiatricum schizophrenia long intergenic non-coding rna lincrna white matter transcriptome brain |
| title | Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain |
| title_full | Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain |
| title_fullStr | Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain |
| title_full_unstemmed | Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain |
| title_short | Dysregulation of Long Intergenic Non-Coding RNA Expression in the Schizophrenia Brain |
| title_sort | dysregulation of long intergenic non coding rna expression in the schizophrenia brain |
| topic | schizophrenia long intergenic non-coding rna lincrna white matter transcriptome brain |
| url | https://consortium-psy.com/jour/article/viewFile/219/pdf |
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