Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia
| Autor: | Michèle Allard, Laura Cif, Gwénaëlle Catheline, Dominique Guehl, Pierre Burbaud, Philippe Fernandez, Marie Vidailhet, Elodie Barse, Delphine Vimont, Bernard Mazoyer, Nicolas Langbour, Bixente Dilharreguy, Frederic Lamare, Bastien Ribot, Marc Deffains, Joachim Mazere, Antonio Pisani |
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| Přispěvatelé: | Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers, Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2021 |
| Předmět: |
Adult
Male 0301 basic medicine Cerebellum Vesicular Acetylcholine Transport Proteins Dystonia Musculorum Deformans Caudate nucleus Young Adult 03 medical and health sciences 0302 clinical medicine Vesicular acetylcholine transporter Humans Medicine Cholinergic neuron Aged Dystonia business.industry [SCCO.NEUR]Cognitive science/Neuroscience Putamen Middle Aged medicine.disease Magnetic Resonance Imaging Corpus Striatum 030104 developmental biology medicine.anatomical_structure Positron-Emission Tomography Cerebellar vermis Cholinergic Female Neurology (clinical) business Neuroscience 030217 neurology & neurosurgery Molecular Chaperones |
| Zdroj: | Brain-A Journal of Neurology Brain-A Journal of Neurology, Oxford University Press (OUP), 2021, 144 (3), pp.909-923. ⟨10.1093/brain/awaa465⟩ |
| ISSN: | 1460-2156 0006-8950 |
| DOI: | 10.1093/brain/awaa465 |
| Popis: | Early-onset torsion dystonia (TOR1A/DYT1) is a devastating hereditary motor disorder whose pathophysiology remains unclear. Studies in transgenic mice suggested abnormal cholinergic transmission in the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms. |
| Databáze: | OpenAIRE |
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