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Huntington’s Disease pp 285–301Cite as

In Vivo Multidimensional Brain Imaging in Huntington’s Disease Animal Models

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1780))

Abstract

Huntington’s disease (HD) is a genetic neurodegenerative disorder caused by an abnormal expansion of a CAG repeat located in the gene encoding for huntingtin protein. This mutation induces the expression of a polyglutamine stretch in the mutated protein resulting in the modification of various biological properties of the wild-type protein and the progressive appearance of motor, cognitive, and psychiatric disorders that are typically associated to this condition. Although the exact neuropathological mechanisms of degeneration are still not fully understood, HD pathology is characterized by severe neuronal losses in various brain regions including the basal ganglia and many cortical areas. Early signs of astrogliosis may precede actual neuronal degeneration. Early metabolic impairment at least in part associated with mitochondrial complex II deficiency may play a key role in huntingtin-induced mechanisms of neurodegeneration. Clinical trials are actively prepared including various gene-silencing approaches aiming at decreasing mutated huntingtin production. However, with the lack of a specific imaging biomarker capable of visualizing mutated huntingtin or huntingtin aggregates, there is a need for surrogate markers of huntingtin neurodegeneration. MRI and caudate nucleus atrophy is one of the most sensitive imaging biomarkers of HD. As such it can be used as a means to study disease progression and potential halting of the neurodegenerative process by therapeutic intervention, but this marker relies on actual neuronal loss which is a somewhat a late event in the pathology. As a means to develop, characterize and evaluate new, potentially earlier biomarkers of HD pathology we have recently embarked on a series of NMR developments looking for brain imaging techniques that allow for noninvasive longitudinal evaluation/characterization of functional alterations in animal models of HD. This chapter describes an assemblage of innovative NMR methods that have proved useful in detecting pathological cell dysfunctions in various preclinical models of HD.

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Acknowledgments

The 11.7 T MRI scanner was funded by a grant from NeurATRIS: A Translational Research Infrastructure for Biotherapies in Neurosciences (“Investissement d’Avenir,” ANR-11-INBS-0011). J.F. and J.V. are recipients of a grant from L’Agence Nationale de la Recherche (“HDeNERGY” project, ANR-14-CE15-0007-01), and J.V. was supported by the European Research Council (“INCELL” project, ERC grant 336331).

Author information

Authors and Affiliations

  1. CEA, DRF, Institut de biologie François Jacob, Molecular Imaging Research Center (MIRCen), Fontenay-aux-Roses, France

    Julien Flament, Philippe Hantraye & Julien Valette

  2. INSERM, US27, Fontenay-aux-Roses, France

    Julien Flament & Philippe Hantraye

  3. CNRS, CEA, Paris-Sud Univ., Univ. Paris-Saclay, Neurodegenerative Diseases Laboratory (UMR9199), Fontenay-aux-Roses, France

    Philippe Hantraye & Julien Valette

Authors
  1. Julien Flament
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  2. Philippe Hantraye
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  3. Julien Valette
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Corresponding author

Correspondence to Philippe Hantraye .

Editor information

Editors and Affiliations

  1. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Sophie V. Precious

  2. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Anne E. Rosser

  3. Brain Repair Group, Cardiff University, Cardiff, United Kingdom

    Stephen B. Dunnett

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Flament, J., Hantraye, P., Valette, J. (2018). In Vivo Multidimensional Brain Imaging in Huntington’s Disease Animal Models. In: Precious, S., Rosser, A., Dunnett, S. (eds) Huntington’s Disease. Methods in Molecular Biology, vol 1780. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7825-0_15

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  • DOI: https://doi.org/10.1007/978-1-4939-7825-0_15

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7824-3

  • Online ISBN: 978-1-4939-7825-0

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