title: Brain Diffusivity and Structural Changes in the R6/2 Mouse Model of Huntington Disease.
abstract: Diffusion-weighted magnetic resonance (DW-MR) is an important diagnostic tool in Huntington disease (HD), a fatal hereditary neurodegenerative disorder. To clarify the nature of diffusivity changes in HD, we compared the apparent diffusion coefficient of water (ADCW) acquired by DW-MR with extracellular space volume fraction α and tortuosity λ, measured by the iontophoretic method in the R6/2 mouse model of HD and in wild-type controls (WT). In anisotropic globus pallidus (GP), diffusion measurements were performed in the mediolateral (x), rostrocaudal (y), and ventrodorsal (z) axes. In HD animals, we detected an increase in ADCWin all axes and larger α than in WT mice. No significant difference between WT and HD mice was found in the values of tortuosity (λx, λy, λz). Despite structural changes in GP, diffusion anisotropy was unaffected in HD mice. Immunohistochemical analysis revealed in HD mice weaker expression of extracellular matrix and a decrease in neuron numbers compared with WT mice. Glial fibrillary acidic protein staining detected astrogliosis-like changes in the morphology of astrocytic processes in HD GP. In the somatosensory cortex, no significant differences in the studied parameters were found. We conclude that in the R6/2 model of HD, a decrease in the number of neurons in the GP results in increased ADCWand α values. Values of λ were not significantly changed as the increase of diffusion obstacles formed by reactive astrocytes was compensated for by the extracellular matrix reduction. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine AS CR, v.v.i., Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Vorisek
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine AS CR, v.v.i., Prague, Czech Republic.|International Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Syka
authors.affiliation: Department of Neuroscience, Institute of Experimental Medicine AS CR, v.v.i., Prague, Czech Republic.|Department of Neuroscience, Charles University, 2nd Faculty of Medicine, Prague, Czech Republic.
authors.forename: Lydia
authors.initials: L
authors.lastname: Vargova
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic
keywords: Research Resource Identifiers; astrogliosis; basal ganglia disorders; extracellular matrix; magnetic resonance imaging; neurodegenerative diseases