Brain 5-HT1A Receptor Binding in Multiple System Atrophy: An [18F]-MPPF PET Study
Marie Meyer MD, PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorFrédéric Lamare PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorJulien Asselineau MSc
Public Health Department, Clinical Epidemiology Unit, Bordeaux University Hospital, Bordeaux, France
Search for more papers by this authorAlexandra Foubert-Samier MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Inserm, UMR1219, Bordeaux Population Health Research Center, Bordeaux University, ISPED, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Search for more papers by this authorJoachim Mazère PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorPaolo Zanotti-Fregonara MD, PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorGaia Rizzo PhD
Invicro and Division of Brain Sciences, Imperial College London, London, UK
Search for more papers by this authorAnna Delamarre MD
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Search for more papers by this authorUmberto Spampinato MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
Search for more papers by this authorOlivier Rascol MD, PhD
French Reference Centre for MSA, University Hospital Toulouse, Toulouse, France
Clinical Investigation Center CIC 1436 and Departments of Neurosciences and Clinical Pharmacology, Inserm, Toulouse University and CHU Toulouse, Toulouse, France
Search for more papers by this authorAnne Pavy-Le Traon MD, PhD
French Reference Centre for MSA, University Hospital Toulouse, Toulouse, France
Institut des Maladies Métaboliques et Cardiovasculaires, Inserm U 1048, Toulouse University, Toulouse, France
Search for more papers by this authorFrançois Tison MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Search for more papers by this authorPhilippe Fernandez MD, PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Deceased.
Search for more papers by this authorIgor Sibon MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
Search for more papers by this authorCorresponding Author
Wassilios G Meissner MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Department of Medicine, University of Otago, Christchurch, and New Zealand Brain Research Institute, Christchurch, New Zealand
*Correspondence to: Prof. Wassilios Meissner, CRMR AMS, Hôpital Pellegrin, CHU Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux cedex, France; E-mail: [email protected]
Search for more papers by this authorMarie Meyer MD, PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorFrédéric Lamare PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorJulien Asselineau MSc
Public Health Department, Clinical Epidemiology Unit, Bordeaux University Hospital, Bordeaux, France
Search for more papers by this authorAlexandra Foubert-Samier MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Inserm, UMR1219, Bordeaux Population Health Research Center, Bordeaux University, ISPED, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Search for more papers by this authorJoachim Mazère PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorPaolo Zanotti-Fregonara MD, PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Search for more papers by this authorGaia Rizzo PhD
Invicro and Division of Brain Sciences, Imperial College London, London, UK
Search for more papers by this authorAnna Delamarre MD
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Search for more papers by this authorUmberto Spampinato MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
Search for more papers by this authorOlivier Rascol MD, PhD
French Reference Centre for MSA, University Hospital Toulouse, Toulouse, France
Clinical Investigation Center CIC 1436 and Departments of Neurosciences and Clinical Pharmacology, Inserm, Toulouse University and CHU Toulouse, Toulouse, France
Search for more papers by this authorAnne Pavy-Le Traon MD, PhD
French Reference Centre for MSA, University Hospital Toulouse, Toulouse, France
Institut des Maladies Métaboliques et Cardiovasculaires, Inserm U 1048, Toulouse University, Toulouse, France
Search for more papers by this authorFrançois Tison MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Search for more papers by this authorPhilippe Fernandez MD, PhD
Service de Médecine Nucléaire, CHU de Bordeaux, Bordeaux, France
Institut des Neurosciences Cognitives et Intégratives d'Aquitaine, CNRS, UMR 5287, Bordeaux University, Bordeaux, France
Deceased.
Search for more papers by this authorIgor Sibon MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
Search for more papers by this authorCorresponding Author
Wassilios G Meissner MD, PhD
Service de Neurologie, CHU Bordeaux, Bordeaux, France
French Reference Centre for MSA, University Hospital Bordeaux, Bordeaux, France
Univ. de Bordeaux, CNRS, IMN, UMR 5293, Bordeaux, F-33000, France, Bordeaux, France
Department of Medicine, University of Otago, Christchurch, and New Zealand Brain Research Institute, Christchurch, New Zealand
*Correspondence to: Prof. Wassilios Meissner, CRMR AMS, Hôpital Pellegrin, CHU Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux cedex, France; E-mail: [email protected]
Search for more papers by this authorRelevant conflicts of interest/financial disclosures: The authors have no conflict of interest regarding the content of this article.
Funding agencies: GIRCI SOHO API 2007.
Abstract
Background
Loss of medullary serotonin (5-hydroxytryptamine) neurons has been linked to respiratory disturbances in multiple system atrophy (MSA). Broader 5-hydroxytryptamine dysfunction may contribute to additional motor/nonmotor symptoms in MSA. The objective of this study was to compare brain 5-hydroxytryptamine1A receptor binding between MSA and healthy controls. Secondary objectives were to compare 5-hydroxytryptamine1A receptor binding between MSA and Parkinson's disease (PD) and to assess potential associations with motor/nonmotor symptoms in MSA.
Methods
2′-Methoxyphenyl-(N-2′-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine positron emission tomography was performed in matched MSA patients (n = 16), PD patients (n = 15), and healthy controls (n = 18).
Results
2′-Methoxyphenyl-(N-2′-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios were lower in MSA patients versus healthy controls in several brain regions including the caudate, raphe nuclei, thalamus, and brain stem. Distribution volume ratios were also lower in brain stem and amygdala in MSA versus PD. Moderate associations were found between 2′-methoxyphenyl-(N-2′-pyridinyl)-p-18F-fluoro-benzamidoethylpiperazine distribution volume ratios and fatigue, pain, and apathy in MSA.
Conclusion
Our results demonstrate 5-hydroxytryptamine dysfunction in several brain regions in MSA, which may contribute to fatigue, pain, and apathy. © 2020 International Parkinson and Movement Disorder Society
Supporting Information
| Filename | Description |
|---|---|
| mds28295-sup-0001-FigureS1.pdfPDF document, 854.1 KB |
FIG. S1. Illustration of the segmented brain atlas of ROIs applied to MR image. |
| mds28295-sup-0002-FigureS2.pdfPDF document, 760.7 KB |
FIG. S2. Illustration of [18F]-MPPF uptake in the raphe nuclei in MSA (A), PD (B), and HC (C). The represented examples show reduced [18F]-MPPF uptake in MSA (A) compared with HC (C). [18F]-MPPF uptake in the raphe nuclei is similar to MSA (A) and PD (B). HC, healthy controls; MSA, multiple system atrophy; PD, Parkinson's Disease; SUV, standard uptake value. |
| mds28295-sup-0003-FigureS3.pdfPDF document, 282.2 KB |
FIG. S3. Moderate correlations between [18F]-MPPF DVR in the raphe nuclei and the brain stem with fatigue (A, C) and pain (B, D), as well as between [18F]-MPPF DVR in the amygdala and apathy (E) in MSA patients. |
| mds28295-sup-0004-TableS1.docxWord 2007 document , 16.2 KB |
TABLE S1. Assessment of potential associations between [18F]-MPPF DVR and clinical rating scales in MSA patients. AI, apathy Inventory; BDI, Beck Depression Inventory; DVR, distribution volume ratio; ESS, Epworth Sleepiness Scale; FSS, Fatigue Severity Scale; MSA, multiple system atrophy; PSQI, Pittsburgh Sleep Quality Index; UMSARS, Unified MSA Rating Scale; 95% CI, 95% confidence interval. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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