Transgenic Rat Model of Huntington’s Disease: A Histopathological Study and Correlations with Neurodegenerative Process in the Brain of HD Patients

Abstract

Rats transgenic for Huntington's disease (tgHD51 CAG rats), surviving up to two years, represent an animal model of HD similar to the late-onset form of human disease. This enables us to follow histopathological changes in course of neurodegenerative process (NDP) within the striatum and compare them with postmortem samples of human HD brains. A basic difference between HD pathology in human and tgHD51 rats is in the rate of NDP progression that originates primarily from slow neuronal degeneration consequently resulting in lesser extent of concomitant reactive gliosis in the brain of tgHD51 rats. Although larger amount of striatal neurons displays only gradual decrease in their size, their number is significantly reduced in the oldest tgHD51 rats. Our quantitative analysis proved that the end of the first year represents the turn in the development of morphological changes related to the progression of NDP in tgHD51 rats. Our data also support the view that all types of CNS glial cells play an important, irreplaceable role in NDP. To the best of our knowledge, our findings are the first to document that tgHD51 CAG rats can be used as a valid animal model for detailed histopathological studies related to HD in human.

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

“…In the GP of HD mice, an increase in α was associated with a profound decrease in the number of neurons. Enlargement of the extracellular volume may be even more pronounced by a decrease in the volume of degenerated neurons, as was reported recently (Mazurova et al, ). This effect might be to some extent compensated for by a loss of extracellular matrix, which is usually related to α decrease (Sykova et al, ) and by a typical atrophy of HD tissue (Aylward et al, ).…”

“…The lack of a decrease in λ can also be explained by the creation of additional diffusion barriers due to gliotic rebuilding of astrocytic processes, which can compensate for the ECM loss. Indeed, astrogliosis has been reported in many studies dealing with the pathogenesis of HD (Lin et al, ; Gu et al, ; Faideau et al, ; Mazurova et al, ). Even if the quantitative analysis in this study did not confirm an increase in GFAP staining or an increased number of astrocytes in HD in comparison with WT mice, gliosis‐related changes of astrocyte morphology are clearly visible as fewer, thicker, and more convoluted processes in the GP in HD animals vs. fine, loosely arranged processes in WT mice (Fig.…”

“…Recent findings indicate that reactive astrocytes in HD, where astrogliosis progresses slowly, differ from those found in the tissue after acute injury or ischemia. In the transgenic rat model of HD, the somata of astrocytes are less hypertrophic and partially degenerated, and enlarged GFAP + vascular endfeet are often found (Mazurova et al, ). Despite the different animal model used in this study, we have also detected the above‐mentioned features of reactive astrocytes in the current study (Fig.…”

Modern approaches for modelling dystonia and Huntington's disease in vitro and in vivo

“…One of the transgenic rat models, tgHD51, carries 51 CAG repeats and survives up to two years. This model represents the late‐onset HD similar to the human disease . Another recent rat model, BACHD, is characterized by progressive neurodegenerative impairments and extensive loss of striatal neurons …”

“…This model represents the late-onset HD similar to the human disease. 49 Another recent rat model, BACHD, is characterized by progressive neurodegenerative impairments and extensive loss of striatal neurons. 50…”