Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression
Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (<i>SNCA</i>), lysosomal enzyme β-glu...
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/6/3219 |
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| author | Razvan-Marius Brazdis Claudia von Zimmermann Bernd Lenz Johannes Kornhuber Christiane Mühle |
| author_facet | Razvan-Marius Brazdis Claudia von Zimmermann Bernd Lenz Johannes Kornhuber Christiane Mühle |
| author_sort | Razvan-Marius Brazdis |
| collection | DOAJ |
| description | Due to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (<i>SNCA</i>), lysosomal enzyme β-glucocerebrosidase (<i>GBA1</i>), and UDP-glucose ceramide glucosyltransferase (<i>UGCG</i>) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated <i>n</i> = 63, medicated <i>n</i> = 66) and controls (remitted MDD <i>n</i> = 39, healthy subjects <i>n</i> = 61). We observed that expression levels of <i>SNCA</i> (<i>p</i> = 0.036), <i>GBA1</i> (<i>p</i> = 0.014), and <i>UGCG</i> (<i>p</i> = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of <i>GBA1</i> and <i>UGCG</i> decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that <i>SNCA</i>, <i>GBA1</i>, and <i>UGCG</i> analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases. |
| first_indexed | 2024-04-24T18:12:25Z |
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| id | doaj.art-6d2fcff38f2848ccba7ade5a7a01ab7a |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T18:12:25Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6d2fcff38f2848ccba7ade5a7a01ab7a2024-03-27T13:45:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01256321910.3390/ijms25063219Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major DepressionRazvan-Marius Brazdis0Claudia von Zimmermann1Bernd Lenz2Johannes Kornhuber3Christiane Mühle4Department of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Psychiatry and Psychotherapy, Universitätsklinikum Erlangen and Friedrich-Alexander University Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDue to the high comorbidity of Parkinson’s disease (PD) with major depressive disorder (MDD) and the involvement of sphingolipids in both conditions, we investigated the peripheral expression levels of three primarily PD-associated genes: α-synuclein (<i>SNCA</i>), lysosomal enzyme β-glucocerebrosidase (<i>GBA1</i>), and UDP-glucose ceramide glucosyltransferase (<i>UGCG</i>) in a sex-balanced MDD cohort. Normalized gene expression was determined by quantitative PCR in patients suffering from MDD (unmedicated <i>n</i> = 63, medicated <i>n</i> = 66) and controls (remitted MDD <i>n</i> = 39, healthy subjects <i>n</i> = 61). We observed that expression levels of <i>SNCA</i> (<i>p</i> = 0.036), <i>GBA1</i> (<i>p</i> = 0.014), and <i>UGCG</i> (<i>p</i> = 0.0002) were higher in currently depressed patients compared to controls and remitted patients, and expression of <i>GBA1</i> and <i>UGCG</i> decreased in medicated patients during three weeks of therapy. Additionally, in subgroups, expression was positively correlated with the severity of depression and anxiety. Furthermore, we identified correlations between the gene expression levels and PD-related laboratory parameters. Our findings suggest that <i>SNCA</i>, <i>GBA1</i>, and <i>UGCG</i> analysis could be instrumental in the search for biomarkers of MDD and in understanding the overlapping pathological mechanisms underlying neuro-psychiatric diseases.https://www.mdpi.com/1422-0067/25/6/3219affective disorderanxietybiomarker<i>GBA1</i>gene expressionmajor depressive disorder |
| spellingShingle | Razvan-Marius Brazdis Claudia von Zimmermann Bernd Lenz Johannes Kornhuber Christiane Mühle Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression International Journal of Molecular Sciences affective disorder anxiety biomarker <i>GBA1</i> gene expression major depressive disorder |
| title | Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression |
| title_full | Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression |
| title_fullStr | Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression |
| title_full_unstemmed | Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression |
| title_short | Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression |
| title_sort | peripheral upregulation of parkinson s disease associated genes encoding α synuclein β glucocerebrosidase and ceramide glucosyltransferase in major depression |
| topic | affective disorder anxiety biomarker <i>GBA1</i> gene expression major depressive disorder |
| url | https://www.mdpi.com/1422-0067/25/6/3219 |
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