Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington’s disease reveals early gray and white matter alterations - Molecular Imaging Research Center Accéder directement au contenu
Article Dans Une Revue Human Molecular Genetics Année : 2022

Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington’s disease reveals early gray and white matter alterations

Marco Palombo
  • Fonction : Auteur
Marc Dhenain
Sandrine Humbert
  • Fonction : Auteur
Emmanuel Brouillet
  • Fonction : Auteur
Julien Flament

Résumé

Abstract Pathogenesis of the inherited neurodegenerative disorder Huntington’s disease (HD) is progressive with a long presymptomatic phase in which subtle changes occur up to 15 years before the onset of symptoms. Thus, there is a need for early, functional biomarker to better understand disease progression and to evaluate treatment efficacy far from onset. Recent studies have shown that white matter may be affected early in mutant HTT gene carriers. A previous study performed on 12 months old Ki140CAG mice showed reduced glutamate level measured by Chemical Exchange Saturation Transfer of glutamate (gluCEST), especially in the corpus callosum. In this study, we scanned longitudinally Ki140CAG mice with structural MRI, diffusion tensor imaging, gluCEST and magnetization transfer imaging, in order to assess white matter integrity over the life of this mouse model characterized by slow progression of symptoms. Our results show early defects of diffusion properties in the anterior part of the corpus callosum at 5 months of age, preceding gluCEST defects in the same region at 8 and 12 months that spread to adjacent regions. At 12 months, frontal and piriform cortices showed reduced gluCEST, as well as the pallidum. MT imaging showed reduced signal in the septum at 12 months. Cortical and striatal atrophy then appear at 18 months. Vulnerability of the striatum and motor cortex, combined with alterations of anterior corpus callosum, seems to point out the potential role of white matter in the brain dysfunction that characterizes HD and the pertinence of gluCEST and DTI as biomarkers in HD.

Domaines

Neurobiologie

Dates et versions

hal-03787296 , version 1 (24-09-2022)

Identifiants

Citer

Jean-Baptiste Pérot, Marina Célestine, Marco Palombo, Marc Dhenain, Sandrine Humbert, et al.. Longitudinal multimodal MRI characterization of a knock-in mouse model of Huntington’s disease reveals early gray and white matter alterations. Human Molecular Genetics, 2022, ⟨10.1093/hmg/ddac036⟩. ⟨hal-03787296⟩
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