Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia

Joachim Mazere, Bixente Dilharreguy, Gwenaëlle Catheline, Marie Vidailhet, Marc Deffains, Delphine Vimont, Bastien Ribot, Elodie Barse, Laura Cif, Bernard Mazoyer, Nicolas Langbour, Antonio Pisani, Michèle Allard, Frédéric Lamare, Dominique Guehl, Philippe Fernandez, Pierre Burbaud

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)909-923
Number of pages15
JournalBrain : a journal of neurology
Volume144
Issue number3
DOIs
Publication statusPublished - Apr 12 2021

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