Click on image to view larger version.
Figure 3. Enhanced dopamine (DA) transmission in a knock-in mouse model of HD containing 92 CAG repeats (DAT–/–,HdhQ92/Q92) exacerbates the deleterious effects of mutated huntingtin protein on striatal function and motor behaviors by accelerating the formation of mutant huntingtin aggregates. Schematic diagrams represent the striatum, globus pallidus, and subtantia nigra of 8-month-old DAT+/+,HdhQ92/Q92 and DAT–/–,HdhQ92/Q92 mice immunostained with EM48 Ab. Nuclear staining (large circular dots) and neuropil aggregates (small oval dots) were not found in the subtantia nigra pars compacta (SNc), which projects to the striatum (STR). In DAT+/+, HdhQ92/Q92, nuclear staining was noticed in only a few cells of the striatum. On the other hand, nuclear staining and neuropil aggregates were both observed in abundance in the striatum of DAT–/–,HdhQ92/Q92 mice. A few nuclear aggregates (asterisks) were also observed in this structure. Neuropil aggregates, but not nuclear aggregates, were found in the globus pallidus (GP) and the subtantia nigra pars reticulata (SNr). These changes in the physical nature of mutant huntingtin were associated with a decline in locomotor behaviors in DAT–/–,HdhQ92/Q92 mice.
