Fig. 8: Re-expression of Scn1a gene in adult mice (P90) rescues seizures in DS mice.
a Schematics depicting the experimental timeline: Scn1aStop/+ mice were implanted with EEG transmitters at P70 and, few days after were video-EEG recorded for 2 weeks (baseline). Mice that experienced at least one seizure over the 2 weeks of recordings were randomized and were administrated with either PHP.eB-Cre or PHP.eB-Ctrl through tail vein injections at P90. Thereafter, video-EEG continued for further 25 days, until mice reached postnatal day 115. Created with BioRender.com. b Raster plot showing all generalized tonic-clonic seizures (Racine scale stages 4 and 5) in 6 Scn1aStop/+-Ctrl injected mice and 6 Scn1aStop/+-Cre mice c Pie chart showing the proportion of Ctrl- and -Cre-injected Scn1aStop/+ mice with an increased or decreased number of seizures compared to baseline after viral delivery (p = 0.0152; two-sided Fisher’s exact test). d Seizure frequency during the baseline period and after viral injection in both Ctrl- and Cre-injected Scn1aStop/+ mice. Seizure frequency in the baseline between the two groups (*p = 0.235, t-test). Seizure frequency before and after viral administration in Scn1aStop/+-Ctrl (p = 0.53, two-way ANOVA with Sidak’s multiple comparison, n = 6) and Scn1aStop/+-Cre; *p = 0.028, two-way ANOVA with Sidak’s multiple comparison, n = 6), e Percentage of Scn1aStop/+-Ctrl and Scn1aStop/+-Cre mice remaining seizure-free after thermal induction (n = 6 for each group, ***p = 0.0002; Mantel-Cox log-rank test). f Pie charts showing the percentage of Scn1aStop/+-Ctrl and for Scn1aStop/+ -Cre mice with or without induced thermal seizures (p = 0.0152; two-sided Fisher’s exact test). Source data are provided as a Source Data file.
