Fig. 6

Tau-targeting ASO rescues autism-like phenotypes in Fmr1^−/y mice. A ASO treatment paradigm. Fmr1^−/y mice (FVB background, 1-month-old) were treated with 25 μg/d ASO-Tau or ASO-NC via intracerebroventricular infusion for 2 weeks and the catheters were then removed. After another 2 weeks, behavioral tests were performed. B–D In the open field test, time spent in the center (B), center entry numbers (C), and total travel distance (D) were analyzed. E, F In the self-grooming test, grooming time (E) and bout numbers (F) were analyzed. G In the nest building test, nesting scores of mice were analyzed. H–J In the three-chamber social interaction test, time spent in each chamber (H), time spent interacting with a Stranger 1 mouse and the empty cage (I), and time spent interacting with the Stranger 1 mouse and a Stranger 2 mouse (J) were analyzed. K In the autonomous wheel-running test, mouse activity was recorded for 5 consecutive days in a constant darkness environment and compared. For behavioral tests in B-J, ASO-NC: n = 10; ASO-Tau: n = 11. For tests in K, ASO-NC: n = 7; ASO-Tau: n = 7. L–O Equal amounts of protein lysates from 2.5-month-old mouse cortical tissues were analyzed by western blotting for indicated proteins (L). Total Tau levels were normalized to those of GAPDH for comparison (M); and levels of phosphorylated P38 (N) and ERK (O) were normalized to respective total protein levels for comparison. ASO-NC: n = 6; ASO-Tau: n = 6. Unpaired t test for (B–G, M–O). Two-way ANOVA followed by Bonferroni’s post hoc test for H-J. Two-way repeated-measures ANOVA for K. ns: not significant, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001