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Publication : Brain Diffusivity and Structural Changes in the R6/2 Mouse Model of Huntington Disease.

First Author  Vorisek I Year  2017
Journal  J Neurosci Res Volume  95
Issue  7 Pages  1474-1484
PubMed ID  27726161 Mgi Jnum  J:347781
Mgi Id  MGI:7625797 Doi  10.1002/jnr.23965
Citation  Vorisek I, et al. (2017) Brain Diffusivity and Structural Changes in the R6/2 Mouse Model of Huntington Disease. J Neurosci Res 95(7):1474-1484
abstractText  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 (ADC(W) ) acquired by DW-MR with extracellular space volume fraction alpha and tortuosity lambda, 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 ADC(W) in all axes and larger alpha than in WT mice. No significant difference between WT and HD mice was found in the values of tortuosity (lambda(x) , lambda(y) , lambda(z) ). 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 ADC(W) and alpha values. Values of lambda were not significantly changed as the increase of diffusion obstacles formed by reactive astrocytes was compensated for by the extracellular matrix reduction. (c) 2016 Wiley Periodicals, Inc.
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