Figure 4
Hippocampal atrophy precedes cerebellar degeneration and reflects the severity of the behavioral deficits. (a) Standardized regression coefficients (β) and 95% confidence intervals (95% CI) for the effect of the SCA1 genotype on brain volumes. The thickness indicates that 95% CI did not cross zero. Cb = cerebellum. CA = Cornu ammonis. DG = dentate gyrus. GL = granular layer. ML = molecular layer. SPO = stratum pyramidale and oriens. SRLM = stratum radiatum and lacunosum-moleculare. PL = polymorph layer. N = 8 animals per group (32 weeks of age). See Suppl. Table S14 for details. (b) Cerebellar molecular/granular layer volume ratio (Cb-ML). (c) CA-SRLM and DG-ML hippocampal volumes. Box-whisker plots (b,c) indicating inter-quartile (IQ) intervals (box), 1.5*IQ range (whiskers) and medians (middle line). Each point = 1 animal. N (b,c) = 8 (WT) and 10 (SCA1) animals (9 per group in case of the youngest cohort). *P < 0.05, **P < 0.01, ***P < 0.001. n.s. = not significant. The P-values are based on the permutational t-test (b,c). (d) β for the effect of the Cb-ML (left) and DG-ML (right) volumes on the sensitive indicators and 95% CI. The thickness indicates that 95% CI did not cross zero. The black lines show the results of the models that included both the WT and SCA1 mice with the genotype as a covariate, whereas the red lines show the results obtained from the SCA1 mice-specific data (Suppl. Tables S17–S24). (e) Relationship between the DG-ML volumes and the sensitive indicators significantly associated with the DG-ML in the SCA1 mice: relative non-moving time during the MWM (D1-D7 average; left), error rate during the flexible phase of the water T-maze test (middle) and the immobility time during the FST (right). The lines indicate model fits and their standard errors. The P-values are based on percentile bootstrapping (Suppl. Tables S20 and S21). Each point = 1 animal. N = 17 (WT) and 19 (SCA1) animals (aged 6–15 weeks; d,e).
