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Pizotifen malate and melatonin ameliorate deleterious phenotypes in C. elegans knockout for C9orf72 orthologue (alfa-1). (A-B) Motor activity of alfa-1(ok3062) and N2 (wild-type) worms measured in liquid medium using automated infrared beam scattering. (A)alfa-1(ok3062) worms exhibit motility impairment after 30 minutes compared to N2 controls, which persists throughout the 600 minutes (10-hour) assay. Data are presented as mean ± SEM; n = 3 technical replicates. (B) Improvement in motor activity of alfa-1(ok3062) worms treated with melatonin or pizotifen malate (PM) compared to untreated controls. Motor activity was measured in 30-minute bins over 180 minutes and expressed as a movement score. Data are presented as mean ± SEM; N = 3 technical replicates, n = 6 repeated measurements per replicate. Two-way ANOVA with Dunnett#39;s post-hoc test. *** p < 0.001, **** p < 0.0001. (C) Kaplan-Meier survival analysis of age-dependent paralysis in alfa-1(ok3062) worms on solid media containing 1% DMSO (untreated), melatonin, or PM. Both compounds significantly delay paralysis compared to untreated controls. p < 0.001 (log-rank Mantel-Cox test); N = 3 plates, n = 60-99 worms per condition. (D) Percentage of alfa-1(ok3062) worms displaying neurodegeneration at 9 days post-adulthood on solid media containing 1% DMSO (untreated), melatonin, or PM. Both compounds significantly reduce neurodegeneration. Kruskal-Wallis test with Dunn’s multiple comparison post-hoc test. * p < 0.05, ** p < 0.01; N = 3-9 worm synchronisation, n = 90-270 worms per condition. Data are presented as mean ± SEM.
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