Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour. - Archive ouverte HAL Access content directly
Journal Articles Brain - A Journal of Neurology Year : 2013

Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour.

(1) , (2, 1) , (1) , (1) , (3) , (4) , (5) , (6) , (6) , (7) , (1) , (2) , (8) , (8, 9) , (10) , (9, 10) , (11) , (12) , (8) , (3) , (4) , (3) , (7) , (6) , (2, 13) , (5) , (6) , (1) , (6) , (1) , (1)
1
2
3
4
5
6
7
8
9
10
11
12
13
Esther Steidl
  • Function : Author
Bruno Buisson
  • Function : Author

Abstract

Myotonic dystrophy type 1 is a complex multisystemic inherited disorder, which displays multiple debilitating neurological manifestations. Despite recent progress in the understanding of the molecular pathogenesis of myotonic dystrophy type 1 in skeletal muscle and heart, the pathways affected in the central nervous system are largely unknown. To address this question, we studied the only transgenic mouse line expressing CTG trinucleotide repeats in the central nervous system. These mice recreate molecular features of RNA toxicity, such as RNA foci accumulation and missplicing. They exhibit relevant behavioural and cognitive phenotypes, deficits in short-term synaptic plasticity, as well as changes in neurochemical levels. In the search for disease intermediates affected by disease mutation, a global proteomics approach revealed RAB3A upregulation and synapsin I hyperphosphorylation in the central nervous system of transgenic mice, transfected cells and post-mortem brains of patients with myotonic dystrophy type 1. These protein defects were associated with electrophysiological and behavioural deficits in mice and altered spontaneous neurosecretion in cell culture. Taking advantage of a relevant transgenic mouse of a complex human disease, we found a novel connection between physiological phenotypes and synaptic protein dysregulation, indicative of synaptic dysfunction in myotonic dystrophy type 1 brain pathology.
Fichier principal
Vignette du fichier
Hernandez_manuscript_revised_Brain_v2.pdf (284.92 Ko) Télécharger le fichier
Vignette du fichier
Hernandez_Figures.pdf (1.26 Mo) Télécharger le fichier
Vignette du fichier
Hernandez_SI_Brain_revised_v2.pdf (524.56 Ko) Télécharger le fichier
Vignette du fichier
Hernandez_Sup_Figures.pdf (19.49 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Origin : Files produced by the author(s)
Format : Other
Format : Other

Dates and versions

inserm-00795195 , version 1 (11-02-2014)

Identifiers

Cite

Oscar Hernández-Hernández, Céline Guiraud-Dogan, Géraldine Sicot, Aline Huguet, Sabrina Luilier, et al.. Myotonic dystrophy CTG expansion affects synaptic vesicle proteins, neurotransmission and mouse behaviour.: Synaptic dysfunction in myotonic dystrophy. Brain - A Journal of Neurology , 2013, 136 (Pt 3), pp.957-70. ⟨10.1093/brain/aws367⟩. ⟨inserm-00795195⟩
410 View
1240 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More