Fig. 4

Lrrk2-deficiency promotes nuclear invaginations during aging. a-c Sample EM images from the striatal cells of 12-month-old Lrrk2^+/+ and Lrrk2^−/− mice (a). Scale bar, 2 μm. The nuclear circularity (b) and the ratio of nuclei containing 0 to 3 invaginations (c) were calculated from the EM images. N = 28 neurons for Lrrk2^+/+ mice. N = 25 neurons for Lrrk2^−/− mice. Unpaired t-test of nuclear circularity, ^***p < 0.0001. d Co-staining of Lamin B and CTIP2 in the striatal sections of 12-month-old Lrrk2^+/+ and Lrrk2^−/− mice. Scale bar, 2 μm. e 3D reconstruction of (d). The white arrow points to a nuclear invagination. f Ratio of SPN nuclei containing ≥1 invagination in Lrrk2^+/+ and Lrrk2^−/− mice at 2 (n = 3 mice per genotype, 30–60 neurons per animal) and 12 (n = 4 and 5 for Lrrk2^+/+ and Lrrk2^−/− mice, respectively; 30–75 neurons per animal), and 24 months of age (n = 5 per genotype; 50–70 neurons per animal). 1way ANOVA analysis with multiple comparisons test, ^*p = 0.0406 (2-month-old Lrrk2^−/− vs. 12-month-old Lrrk2^−/− samples), ^*p = 0.0275 (12-month-old Lrrk2^−/− samples vs. 24-month-old Lrrk2^−/− samples). 2way ANONVA analysis with multiple comparisons test, ^***p = 0.0004 (12-month-old Lrrk2^+/+ vs. 12-month-old Lrrk2^−/− samples), ^****p < 0.0001 (24-month-old Lrrk2^+/+ vs. 24-month-old Lrrk2^−/− samples). g Co-staining of CTIP2, LaminB, TOM20, and DAPI in the striatal section of 24-month-old Lrrk2^−/− mice. The arrow points to the mitochondria inside the mouth of nuclear invagination. Scale bar, 5 μm