Fig. 4

Knockdown of circMETTL9 ameliorates neurological dysfunction, cognitive impairment, and nerve cell apoptosis Induced by TBI. A Knockdown of circMETTL9 accelerates functional recovery according to mNSS evaluation on days 1, 3, and 7 post-TBI (Sham, n = 7; TBI, n = 7; AAV2/9-shNC + TBI, n = 8; AAV2/9-shcircMETTL9 + TBI, n = 10). ****P < 0.0001 vs. the sham group; ^###P < 0.001 and ^####P < 0.0001 vs. TBI group; ^$$P < 0.01 and ^$$$P < 0.001 compared to the AAV2/9-shNC group (all by two-way repeated measures ANOVA). B–D Knockdown of circMETTL9 improves spatial learning and memory after TBI. B Typical swimming paths in the Morris water maze during the training trials and probe trial. C Escape latencies to find a hidden platform (an index of spatial learning). *P < 0.05, **P < 0.01 and ***P < 0.001 by two-way repeated measures ANOVA. D Number of platform crossings (an indicator of spatial memory) (Sham, n = 7; TBI, n = 7; AAV2/9-shNC + TBI, n = 8; AAV2/9-shcircMETTL9 + TBI, n = 10). **P < 0.01 by one-way ANOVA. E Left panel: TUNEL staining showing that circMETTL9 knockdown ameliorates nerve cell apoptosis on the 7th day post-TBI. Scale bar = 50 µm. Right panel: Quantification of relative apoptosis rate (n = 3 per group). *P < 0.05, **P < 0.01, and ***P < 0.001 by one-way ANOVA