Figure 8. Single dose ASO treatment alleviates age-dependent behavioral deficits in C9ORF72 mice expressing 450 repeats.
(A) Schematic of the experimental procedure for a single dose ASO targeting degradation of the sense strand C9ORF72 RNA in 9 month old C9450B mice. (B) Expression of repeat-containing C9ORF72 RNAs was determined by qRT-PCR 2 weeks after injection of ASO5 or control ASO (n=6 per group). (C–D) Anxiety-related behaviors determined by (C) marble burying test and (D) elevated plus maze in 12 and 15 month old WT and C9450B mice treated with either control ASO or ASO5 (n=5–7 per group). (E–F) Cognition-related behaviors determined on (E) a Barnes maze and (F) a radial maze in 12 and 15 month old WT and C9450B mice treated with either control ASO or ASO5 (n=10–13 per group). (G) Expression of repeat-containing C9ORF72 RNAs and (H) levels of poly(GP) or poly(GA) proteins in the cortex of 16 month old C9450B mice treated at 9 months with ASO5 or control ASO. Error bars represent s.e.m. Error bars represent s.e.m in biological replicates * p<0.05, ** p<0.01, n.s. not significant, using student t test.