Figure 2

Intranasal administration of NPY reduces cerebellar neuropathology. Eight weeks after beginning of intranasal NPY administration MJD Tg animals were sacrificed for histological analysis. (A,B) Sagittal cresyl violet-stained sections displaying cerebellar granular and molecular layers from Tg + vehicle (A) and Tg + NPY (B). Quantification analysis of the granular and molecular layers length revealed NPY treatment prevented the reduction of granular layer thickness in lobules V and IX ((C), *p < 0.05, n = 10), while no difference in molecular layer thickness was observed. (D–G) Immunostaining of mutant ataxin-3 with an anti-HA antibody, revealing Purkinje cells. Tg mice treated with intranasal NPY presented a higher amount of Purkinje cells (*p < 0.05, n = 5–8) than controls, as quantified in (H). Some Purkinje cells exhibited mutant ataxin-3 aggregates (arrows). A reduction in the number of aggregates in Purkinje cells was observed in Tg treated with NPY when compared to control animals (*p < 0.05, n = 6–9), as quantified in (I). Data are expressed as mean ± SEM. Statistical significance was evaluated with two-way ANOVA followed by Sidak’s post hoc test (C) and with unpaired Student’s t-test (H,I). Scale bars: 500 μm and magnification 100 μm (A,B), and 50 μm (D–G).