Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis
Abstract Background Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manne...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-021-01285-9 |
| _version_ | 1818985809315889152 |
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| author | Timea Aczél Tamás Körtési József Kun Péter Urbán Witold Bauer Róbert Herczeg Róbert Farkas Krisztián Kovács Barna Vásárhelyi Gellért B. Karvaly Attila Gyenesei Bernadett Tuka János Tajti László Vécsei Kata Bölcskei Zsuzsanna Helyes |
| author_facet | Timea Aczél Tamás Körtési József Kun Péter Urbán Witold Bauer Róbert Herczeg Róbert Farkas Krisztián Kovács Barna Vásárhelyi Gellért B. Karvaly Attila Gyenesei Bernadett Tuka János Tajti László Vécsei Kata Bölcskei Zsuzsanna Helyes |
| author_sort | Timea Aczél |
| collection | DOAJ |
| description | Abstract Background Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manner during and between attacks. Methods Twenty-four patients with migraine were recruited and blood samples were collected in a headache-free (interictal) period and during headache (ictal) to investigate disease- and headache-specific alterations. Control samples were collected from 13 age- and sex-matched healthy volunteers. RNA was isolated from PBMCs and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Plasma metabolomic measurement was performed with the Biocrates MxP Quant 500 Kit. Results We identified 144 differentially-expressed genes in PBMCs between headache and headache-free samples and 163 between symptom-free patients and controls. Network analysis revealed that enriched pathways included inflammation, cytokine activity and mitochondrial dysfunction in both headache and headache-free samples compared to controls. Plasma lactate, succinate and methionine sulfoxide levels were higher in migraineurs while spermine, spermidine and aconitate were decreased during attacks. Conclusions It is concluded that enhanced inflammatory and immune cell activity, and oxidative stress can play a role in migraine susceptibility and headache generation. |
| first_indexed | 2024-12-20T18:40:48Z |
| format | Article |
| id | doaj.art-4e582f4b875e4999852267a1d5e6ee40 |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-12-20T18:40:48Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-4e582f4b875e4999852267a1d5e6ee402022-12-21T19:29:48ZengBMCThe Journal of Headache and Pain1129-23691129-23772021-10-0122111810.1186/s10194-021-01285-9Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysisTimea Aczél0Tamás Körtési1József Kun2Péter Urbán3Witold Bauer4Róbert Herczeg5Róbert Farkas6Krisztián Kovács7Barna Vásárhelyi8Gellért B. Karvaly9Attila Gyenesei10Bernadett Tuka11János Tajti12László Vécsei13Kata Bölcskei14Zsuzsanna Helyes15Department of Pharmacology and Pharmacotherapy, Molecular Pharmacology Research Group and Centre for Neuroscience, University of Pécs Szentágothai Research Centre, University of Pécs Medical SchoolDepartment of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of SzegedDepartment of Pharmacology and Pharmacotherapy, Molecular Pharmacology Research Group and Centre for Neuroscience, University of Pécs Szentágothai Research Centre, University of Pécs Medical SchoolSzentágothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of PécsSzentágothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of PécsSzentágothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of PécsDepartment of Laboratory Medicine, Semmelweis UniversityDepartment of Laboratory Medicine, Semmelweis UniversityDepartment of Laboratory Medicine, Semmelweis UniversityDepartment of Laboratory Medicine, Semmelweis UniversitySzentágothai Research Centre, Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, University of PécsDepartment of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of SzegedDepartment of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of SzegedDepartment of Neurology, Interdisciplinary Excellence Centre, Faculty of Medicine, Albert Szent-Györgyi Clinical Center, University of SzegedDepartment of Pharmacology and Pharmacotherapy, Molecular Pharmacology Research Group and Centre for Neuroscience, University of Pécs Szentágothai Research Centre, University of Pécs Medical SchoolDepartment of Pharmacology and Pharmacotherapy, Molecular Pharmacology Research Group and Centre for Neuroscience, University of Pécs Szentágothai Research Centre, University of Pécs Medical SchoolAbstract Background Recent data suggest that gene expression profiles of peripheral white blood cells can reflect changes in the brain. We aimed to analyze the transcriptome of peripheral blood mononuclear cells (PBMC) and changes of plasma metabolite levels of migraineurs in a self-controlled manner during and between attacks. Methods Twenty-four patients with migraine were recruited and blood samples were collected in a headache-free (interictal) period and during headache (ictal) to investigate disease- and headache-specific alterations. Control samples were collected from 13 age- and sex-matched healthy volunteers. RNA was isolated from PBMCs and single-end 75 bp RNA sequencing was performed using Illumina NextSeq 550 instrument followed by gene-level differential expression analysis. Functional analysis was carried out on information related to the role of genes, such as signaling pathways and biological processes. Plasma metabolomic measurement was performed with the Biocrates MxP Quant 500 Kit. Results We identified 144 differentially-expressed genes in PBMCs between headache and headache-free samples and 163 between symptom-free patients and controls. Network analysis revealed that enriched pathways included inflammation, cytokine activity and mitochondrial dysfunction in both headache and headache-free samples compared to controls. Plasma lactate, succinate and methionine sulfoxide levels were higher in migraineurs while spermine, spermidine and aconitate were decreased during attacks. Conclusions It is concluded that enhanced inflammatory and immune cell activity, and oxidative stress can play a role in migraine susceptibility and headache generation.https://doi.org/10.1186/s10194-021-01285-9MigraineTranscriptomic analysisPeripheral blood mononuclear cellsCytokinesMitochondrial dysfunction |
| spellingShingle | Timea Aczél Tamás Körtési József Kun Péter Urbán Witold Bauer Róbert Herczeg Róbert Farkas Krisztián Kovács Barna Vásárhelyi Gellért B. Karvaly Attila Gyenesei Bernadett Tuka János Tajti László Vécsei Kata Bölcskei Zsuzsanna Helyes Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis The Journal of Headache and Pain Migraine Transcriptomic analysis Peripheral blood mononuclear cells Cytokines Mitochondrial dysfunction |
| title | Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis |
| title_full | Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis |
| title_fullStr | Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis |
| title_full_unstemmed | Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis |
| title_short | Identification of disease- and headache-specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis |
| title_sort | identification of disease and headache specific mediators and pathways in migraine using blood transcriptomic and metabolomic analysis |
| topic | Migraine Transcriptomic analysis Peripheral blood mononuclear cells Cytokines Mitochondrial dysfunction |
| url | https://doi.org/10.1186/s10194-021-01285-9 |
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