Authors
Jessica J. Steventon
Rebecca C. Trueman
Da Ma
Emma Yhnell
Zubeyde Bayram-Weston
Marc Modat
Jorge Cardoso
Sebastian Ourselin
Mark Lythgoe
Andrew Stewart
Anne E. Rosser
Derek Kenton Jones, Australian Catholic University
Publication Date
2016
Publication Details
Steventon, J. J, Trueman, R. C, Ma, D., Yhnell, E., Bayram-Weston, Z., Modat, M., Cardoso, J., Ourselin, S., Lythgoe, M., Stewart, A., Rosser, A. E & Jones, DK. (2016). Longitudinal in vivo MRI in a Huntington's disease mouse model: Global atrophy in the absence of white matter microstructural damage. Scientific Reports,6 1-12. United Kingdom: Nature Publishing Group. Retrieved from https://doi.org/10.1038/srep32423
Abstract
Huntington’s disease ( HD ) is a genetically-determined neurodegenerative disease. Characterising neuropathology in mouse models of HD is commonly restricted to cross-sectional ex vivo analyses, beset by tissue fixation issues. In vivolongitudinal magnetic resonance imaging ( MRI ) allows for disease progression to be probed non-invasively. In the HdhQ150 mouse model of HD, in vivo MRI was employed at two time points, before and after the onset of motor signs, to assess brain macrostructure and white matter microstructure. Ex vivoMRI, immunohistochemistry, transmission electron microscopy and behavioural testing were also conducted. Global brain atrophy was found in HdhQ150 mice at both time points, with no neuropathological progression across time and a selective sparing of the cerebellum. In contrast, no white matter abnormalities were detected from the MRI images or electron microscopy images alike. The relationship between motor function and MR-based structural measurements was different for the HdhQ150 and wild-type mice, although there was no relationship between motor deficits and histopathology. Widespread neuropathology prior to symptom onset is consistent with patient studies, whereas the absence of white matter abnormalities conflicts with patient data. The myriad reasons for this inconsistency require further attention to improve the translatability from mouse models of disease.
Document Type
Open Access Journal Article
Access Rights
Open Access
Notes
© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/