Inhibition of the Striatal Specific Phosphodiesterase PDE10A Ameliorates Striatal and Cortical Pathology in R6/2 Mouse Model of Huntington's Disease
Figure 4
Effects of TP-10 treatment on striatal atrophy in R6/2 mice at 13 weeks of age.
(A) Transmitted light microscope images showing representative Nissl-stained coronal sections of a wild-type mouse, a vehicle treated R6/2 mouse and a TP10-treated R6/2 mouse, (left to right, respectively). Marked gross atrophy and enlarged lateral ventricles are present in the sections from the vehicle treated R6/2 mouse compared the wild type mouse. These differences are largely absence from the sections of the R6/2 mouse treated with TP-10 from 4 to 13 weeks of age. (B) Quantification of differences in striatal area. Striatal area was calculated (see Methods) from sections taken from wild type and vehicle- or TP-10 treated R6/2 mice (n = 6/group). An one-ANOVA indicated an overall significant effect of group (F (2,24) = 62.66; p<0.0000). Post hoc analysis indicated that R6/2 mice treated with vehicle had a significantly reduced striatal area compared to the wild type group. The striatal area of R6/2 mice treated with TP-10 was significantly greater than that of the vehicle treated R6/2 mice (p<0.00014), yet significantly smaller than that of the wild type mice (p<0.00013). (C) Quantification of differences in striatal volume in the same groups as (B). An ANOVA indicated an overall significant effect of group (F (2,5) = 7,14; p<0.03). Post hoc analysis indicated that R6/2 mice treated with vehicle had a significantly reduced striatal volume compared to the wild type group. The striatal volume of R6/2 animals treated with TP-10 was intermediate between these two groups, and was significantly greater than that of the vehicle treated R6/2 mice (p<0.03), yet significantly smaller than that of the wildtype mice (p<0.03).