Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome
Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a s...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999612300267X |
| _version_ | 1797731174624264192 |
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| author | Ahmad Seif Kanaan Dongmei Yu Riccardo Metere Andreas Schäfer Torsten Schlumm Berkin Bilgic Alfred Anwander Carol A. Mathews Jeremiah M. Scharf Kirsten Müller-Vahl Harald E. Möller |
| author_facet | Ahmad Seif Kanaan Dongmei Yu Riccardo Metere Andreas Schäfer Torsten Schlumm Berkin Bilgic Alfred Anwander Carol A. Mathews Jeremiah M. Scharf Kirsten Müller-Vahl Harald E. Möller |
| author_sort | Ahmad Seif Kanaan |
| collection | DOAJ |
| description | Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron‑sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes. |
| first_indexed | 2024-03-12T11:55:10Z |
| format | Article |
| id | doaj.art-a201deedc1a74284a6ca033aa2163b69 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-12T11:55:10Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-a201deedc1a74284a6ca033aa2163b692023-08-31T05:00:29ZengElsevierNeurobiology of Disease1095-953X2023-09-01185106252Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndromeAhmad Seif Kanaan0Dongmei Yu1Riccardo Metere2Andreas Schäfer3Torsten Schlumm4Berkin Bilgic5Alfred Anwander6Carol A. Mathews7Jeremiah M. Scharf8Kirsten Müller-Vahl9Harald E. Möller10Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany; Corresponding authors at: Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1A, 04103 Leipzig, Germany.Center for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USAMax Planck Institute for Human Cognitive and Brain Sciences, Leipzig, GermanyMax Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Siemens Healthcare GmbH, Diagnostic Imaging, Magnetic Resonance, Research and Development, Erlangen, GermanyMax Planck Institute for Human Cognitive and Brain Sciences, Leipzig, GermanyHarvard Medical School, Boston, MA, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA; Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, USAMax Planck Institute for Human Cognitive and Brain Sciences, Leipzig, GermanyDepartment of Psychiatry, Center for OCD, Anxiety, and Related Disorders, College of Medicine, University of Florida, Gainesville, FL, USACenter for Human Genetics Research, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USADepartment of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, GermanyMax Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Corresponding authors at: Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstraße 1A, 04103 Leipzig, Germany.Gilles de la Tourette syndrome (GTS) is a neuropsychiatric movement disorder with reported abnormalities in various neurotransmitter systems. Considering the integral role of iron in neurotransmitter synthesis and transport, it is hypothesized that iron exhibits a role in GTS pathophysiology. As a surrogate measure of brain iron, quantitative susceptibility mapping (QSM) was performed in 28 patients with GTS and 26 matched controls. Significant susceptibility reductions in the patients, consistent with reduced local iron content, were obtained in subcortical regions known to be implicated in GTS. Regression analysis revealed a significant negative association of tic scores and striatal susceptibility. To interrogate genetic mechanisms that may drive these reductions, spatially specific relationships between susceptibility and gene-expression patterns from the Allen Human Brain Atlas were assessed. Correlations in the striatum were enriched for excitatory, inhibitory, and modulatory neurochemical signaling mechanisms in the motor regions, mitochondrial processes driving ATP production and iron‑sulfur cluster biogenesis in the executive subdivision, and phosphorylation-related mechanisms affecting receptor expression and long-term potentiation in the limbic subdivision. This link between susceptibility reductions and normative transcriptional profiles suggests that disruptions in iron regulatory mechanisms are involved in GTS pathophysiology and may lead to pervasive abnormalities in mechanisms regulated by iron-containing enzymes.http://www.sciencedirect.com/science/article/pii/S096999612300267XGene expressionIronMagnetic susceptibilityMRISubcortical brainTourette syndrome |
| spellingShingle | Ahmad Seif Kanaan Dongmei Yu Riccardo Metere Andreas Schäfer Torsten Schlumm Berkin Bilgic Alfred Anwander Carol A. Mathews Jeremiah M. Scharf Kirsten Müller-Vahl Harald E. Möller Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome Neurobiology of Disease Gene expression Iron Magnetic susceptibility MRI Subcortical brain Tourette syndrome |
| title | Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome |
| title_full | Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome |
| title_fullStr | Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome |
| title_full_unstemmed | Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome |
| title_short | Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome |
| title_sort | convergent imaging transcriptomic evidence for disturbed iron homeostasis in gilles de la tourette syndrome |
| topic | Gene expression Iron Magnetic susceptibility MRI Subcortical brain Tourette syndrome |
| url | http://www.sciencedirect.com/science/article/pii/S096999612300267X |
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