Figure 7. Cerebellar phenotype characterization in APP/PS1 mouse model.

(A) Immunohistochemical analysis of cerebella from representative APPsw/PS1Δ9 mice at 24 weeks old and 36 weeks old, using 6E10 antibody for detecting Aβ plaques and calbindin antibody as a PC marker. 36-week-old C57BL/6 mice were used as control. Only 36-week-old APPsw/PS1Δ9 mice showed scarce Aβ pathology. Scale bar: 100 μm. (B) Ultrastructural analysis of mitochondria (arrows) present in PCs from representative 24- and 36-week-old APPsw/PS1Δ9 mice. Dense abnormal mitochondria were observed in 36-week-old APPsw/PS1Δ9 mice. Scale bar: 1 μm. (C) Motor performance and cue discrimination parameters in APPsw/PS1Δ9 mice. The average steptimes (± SEM) were measured in 22- to 24-week-old controls (blue; n = 12) and APPsw/PS1Δ9 mice (red; n = 8) on the ErasmusLadder before (t5pre–t8pre) and after (t5post–t8post) perturbations were introduced during sessions 5 to 8. Both before and after the perturbations the steptimes were significantly longer in the mutants (**P < 0.01, ***P < 0.001, respectively; 1-way ANOVA test). (D and E) Extracellular PC activity in awake mice was studied in the cerebellar lobules involved in locomotion (i.e., lobules I–V). Average firing frequencies of both simple spikes and complex spikes measured in APPsw/PS1Δ9 mice (22 weeks of age, n = 35 cells) compared with controls (n = 25 cells). Frequency and regularity of simple spike firing and complex spike firing were measured in PCs. Note that the simple spike firing frequency was significantly lower in APPsw/PS1Δ9 mice, but regularity and complex spike firing frequency were not affected. *P < 0.001, data are mean ± SEM, unpaired Student’s t test.