Pharmacological Characterization of an Antisense Knockdown Zebrafish Model of Dravet Syndrome: Inhibition of Epileptic Seizures by the Serotonin Agonist Fenfluramine
Fig 7
Effect of fenfluramine and sodium valproate on polyspiking discharges recorded from 5 dpf-ATG MO- and CTRL MO-injected larvae.
(A) Representative electrographic activities recorded in CTRL MO larvae incubated with vehicle (VHC), 50 μM fenfluramine (FA) or 100 μM sodium valproate (VPA). (B) Representative electrographic activities recorded in ATG MO-injected larvae incubated with the same compounds. (C1) Occurrence of polyspiking discharges recorded in ATG MO-injected larvae after treatment with VHC, 50 μM FA and 100 μM VPA in all larvae. (C2) Cumulative durations of polyspiking discharges recorded in ATG MO-injected larvae after treatment with VHC, 50 μM FA and 100 μM VPA in all larvae. (ATG MO + FA: 0.2±0.2 events and 88±88 msec/10-min recording; ATG MO + VPA: 0.7±0.7 events and 165±165 msec/10-min recording, n = 20 and 10 larvae, respectively) compared to VHC-treated larvae (ATG MO + VHC: 9.16±2.36 events and 3533±1113 msec/10-min recording; n = 12 larvae; (C3) Mean durations of polyspiking discharges recorded in ATG MO-injected larvae after treatment with VHC, 50 μM FA and 100 μM VPA in seizure-positive larvae (ATG MO + VHC: 385.4±34.1 msec; ATG MO + FA: 439.9±33.2 msec; ATG MO + VPA: 235.7±33.2 msec; n = 110, 4 and 7 events analyzed, respectively). Statistical analysis was performed using Student’s unpaired t-test or Mann–Whitney test for data that failed the normality test, as appropriate. Error bars on all graphs represent standard error of mean (SEM). *** P≤0.001, **** P≤0.0001.