Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Brain - A Journal of Neurology Année : 2021

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

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

Résumé

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.

Domaines

Neurosciences

Dates et versions

hal-03481871 , version 1 (15-12-2021)

Identifiants

Citer

Joachim Mazere, Bixente Dilharreguy, Gwenaëlle Catheline, Marie Vidailhet, Marc Deffains, et al.. Striatal and cerebellar vesicular acetylcholine transporter expression is disrupted in human DYT1 dystonia. Brain - A Journal of Neurology , 2021, 144 (3), pp.909-923. ⟨10.1093/brain/awaa465⟩. ⟨hal-03481871⟩
17 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More