melatonin  (Takeda)

Journal: PLOS One

Article Title: Characterization of a C9orf72 Knockout Danio rerio model for ALS and cross-species validation of potential therapeutics screened in Caenorhabditis elegans

doi: 10.1371/journal.pone.0346613

Figure Lengend Snippet: (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.

Article Snippet: The compounds tested were pizotifen malate (PM, Cayman Chemical; #20765−500) and melatonin (Cayman Chemical; #14427).

Techniques: Activity Assay, Comparison

Journal: PLOS One

Article Title: Characterization of a C9orf72 Knockout Danio rerio model for ALS and cross-species validation of potential therapeutics screened in Caenorhabditis elegans

doi: 10.1371/journal.pone.0346613

Figure Lengend Snippet: (A) Mean swimming distance per minute for pizotifen malate 0.5 µM (PM) treated (+) and untreated (-) C9orf72 +/+ , C9orf72 -/+ , and C9orf72 -/- six day post-fertilization (dpf) zebrafish larvae under a 120-minute phasic dark-light program. Data are presented as mean ± SEM. (B) Quantitative analysis of total swimming distance shows significant increases in PM-treated (+) C9orf72 +/+ and C9orf72 -/- larvae compared to untreated (-) controls. Data are presented as mean ± SEM. Welch and Brown-Forsythe ANOVA with Dunnett#39;s T3 multiple comparisons post-hoc test. **** p < 0.0001 , ** p ≤ 0.01 , NS p > 0.05 . Boxplot extremities indicate minimum and maximum values; box limits represent the central 50% of the data, and the central line marks the median. (C-E) Swimming distance per minute and representative 60-second swimming tracks for treated and untreated C9orf72 +/+ (C) , C9orf72 -/+ (D ), and C9orf72 -/- (E) larvae. Data are presented as mean ± SEM. N = 5, experimental repeats; n = 80, larvae per genotype. Scale bars = 0.2 cm.

Article Snippet: The compounds tested were pizotifen malate (PM, Cayman Chemical; #20765−500) and melatonin (Cayman Chemical; #14427).

Techniques: