Fig. 3
Neuroprotective effects of siRNAp11 in the SOD1-G93A mouse model of ALS. a In situ hybridization (ISH, from the Allen Brain Atlas) and immunohistochemistry (ICH) showing the expression pattern of p11 in the lumbar spinal cord of adult wild-type mice. b, c Confocal images of lumbar spinal cords immunolabeled for p11 and the MN marker SMI32 b or the astroglial marker GFAP c. d mRNA (left) and protein (right) levels of p11 and TASK1 in the spinal cord of SOD1-G93A mice and their Non-Tg littermates, at the indicated stages (see schematic on top). e p11 immunofluorescence (left) and mean intensity (arbitrary units, a.u.; right) of labeling in lumbar MNs of indicated mice and age. MNs were identified as in b. f Confocal images showing astroglial reaction in the ventral horn of SOD1-G93A mice. Double immunolabeling reported p11-immunoreactive astrocytes in the boxed area. g Schematic of timing for injection system implantation and cRNA/siRNAp11 administration. h p11 immunohistochemistry performed in lumbar spinal cord sections obtained from indicated mice which received cRNA or siRNAp11 from P60. Insets, examples of two vacuolated MNs with different levels of p11 immunostaining. i Number of SMI32-identified MNs in the L3–L5 spinal cord segments of 4-month-old mice with the indicated genotypes that received the stated treatments beginning at P60. The box indicates the area of the ventral horn containing the MN pools that were quantified. Scale bars, b, c, e, 50 μm; a, c, 100 μm; h, i, 300 μm. j–l Cumulative probability curves of symptom onset j, survival l, and time course of mean body weight k for cRNA-treated and siRNAp11-treated SOD1-G93A mice. Number of independent samples in each group is in parentheses. Statistic outputs are displayed in plots. Error bars, SEM. *p < 0.05, **p < 0.01, ***p < 0.001; n.s., not significant; by Student t-test d, e, i or two-way ANOVA with post hoc Holm–Sidak method k. Log-Rank test, Kaplan–Meier analysis was applied to j and l. Source data are provided as a Source Data file
