Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage

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 vivo longitudinal magnetic resonance imaging (MRI) allows for disease p...

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Main Authors:	Steventon, Jessica J., Trueman, Rebecca C., Ma, Da, Yhnell, Emma, Bayram-Weston, Zubeyde, Modat, Marc, Cardoso, Jorge, Ourselin, Sebastian, Lythgoe, Mark, Stewart, Andrew J., Rosser, Anne E., Jones, Derek K.
Format:	Article
Language:	English
Published:	Nature Publishing Group 2016
Online Access:	http://eprints.nottingham.ac.uk/38799/ http://eprints.nottingham.ac.uk/38799/ http://eprints.nottingham.ac.uk/38799/ http://eprints.nottingham.ac.uk/38799/1/Steventon%20et%20al%202016.pdf

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spelling	nottingham-387992017-10-14T07:57:52Z http://eprints.nottingham.ac.uk/38799/ Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage Steventon, Jessica J. Trueman, Rebecca C. Ma, Da Yhnell, Emma Bayram-Weston, Zubeyde Modat, Marc Cardoso, Jorge Ourselin, Sebastian Lythgoe, Mark Stewart, Andrew J. Rosser, Anne E. Jones, Derek K. 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 vivo longitudinal 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 vivo MRI, 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 an elective 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. Nature Publishing Group 2016-09-01 Article PeerReviewed application/pdf en cc_by http://eprints.nottingham.ac.uk/38799/1/Steventon%20et%20al%202016.pdf Steventon, Jessica J. and Trueman, Rebecca C. and Ma, Da and Yhnell, Emma and Bayram-Weston, Zubeyde and Modat, Marc and Cardoso, Jorge and Ourselin, Sebastian and Lythgoe, Mark and Stewart, Andrew J. and Rosser, Anne E. and Jones, Derek K. (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 (32423). pp. 1-12. ISSN 2045-2322 http://www.nature.com/articles/srep32423 doi:10.1038/srep32423 doi:10.1038/srep32423
repository_type	Digital Repository
institution_category	Local University
institution	University of Nottingham Malaysia Campus
building	Nottingham Research Data Repository
collection	Online Access
language	English
description	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 vivo longitudinal 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 vivo MRI, 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 an elective 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.
format	Article
author	Steventon, Jessica J. Trueman, Rebecca C. Ma, Da Yhnell, Emma Bayram-Weston, Zubeyde Modat, Marc Cardoso, Jorge Ourselin, Sebastian Lythgoe, Mark Stewart, Andrew J. Rosser, Anne E. Jones, Derek K.
spellingShingle	Steventon, Jessica J. Trueman, Rebecca C. Ma, Da Yhnell, Emma Bayram-Weston, Zubeyde Modat, Marc Cardoso, Jorge Ourselin, Sebastian Lythgoe, Mark Stewart, Andrew J. Rosser, Anne E. Jones, Derek K. Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
author_facet	Steventon, Jessica J. Trueman, Rebecca C. Ma, Da Yhnell, Emma Bayram-Weston, Zubeyde Modat, Marc Cardoso, Jorge Ourselin, Sebastian Lythgoe, Mark Stewart, Andrew J. Rosser, Anne E. Jones, Derek K.
author_sort	Steventon, Jessica J.
title	Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
title_short	Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
title_full	Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
title_fullStr	Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
title_full_unstemmed	Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
title_sort	longitudinal in vivo mri in a huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage
publisher	Nature Publishing Group
publishDate	2016
url	http://eprints.nottingham.ac.uk/38799/ http://eprints.nottingham.ac.uk/38799/ http://eprints.nottingham.ac.uk/38799/ http://eprints.nottingham.ac.uk/38799/1/Steventon%20et%20al%202016.pdf
first_indexed	2018-09-06T12:54:41Z
last_indexed	2018-09-06T12:54:41Z
_version_	1610862802416697344

Longitudinal in vivo MRI in a Huntington’s disease mouse model: global atrophy in the absence of white matter microstructural damage

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