Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism
Fig 1
Lethality and spontaneous recurrent seizures in adult Cyfip2+/R87C mice.
(A) Survival curves of Cyfip2+/R87C mice (on the C57BL/6N (N) background), Cyfip2+/− mice (on either the C57BL/6N or C57BL/6J (J) backgrounds), and their respective wild-type (WT) littermates, tracked from postnatal weeks 3 to 30 (log-rank test). (B) Behavioral seizure events during long-term (5-day) video recordings of Cyfip2+/R87C mice at postnatal weeks 14 (PWK 14) and 28 (PWK 28) (each group includes four mice, N1 to N4). Arrowheads indicate one-hour recording sessions with either one (black) or multiple (red) seizure events. Cyfip2+/R87C mouse N2 of PWK 28 died on day 5 of recording. The pie charts show the distribution of the number of seizure events per one-hour session at PWK 14 and PWK 28 (Fisher’s exact test). The line chart displays the number of seizure events during the 5-day recording for each genotype. Thin lines represent individual mice, while thick lines indicate the group averages. Note that no seizure events were observed in WT or Cyfip2+/− mice at PWK 28 (n = 4 mice per genotype). (C) Representative traces of EEG recordings from WT and Cyfip2+/R87C mice at PWK 20. Graphs show quantifications of the total number of seizures, tonic-clonic (T-C) seizures, and myoclonic jerks, as well as the duration (dur.) of T-C seizures and the amplitude (amp.) of myoclonic jerks (n = 3 mice per genotype, unpaired two-tailed Student t test). (D) Representative fluorescence immunohistochemistry images and quantification show a reduction in the CA1 region and dispersion of the dentate gyrus (DG) granule cell layer (GCL) in the hippocampus of Cyfip2+/R87C mice compared to WT mice at PWK 28 (n = 7 to 9 mice per genotype, two-way ANOVA with Šídák’s multiple comparisons test). Cyfip2+/− mice displayed a normal hippocampus, except for a reduction in DG height (H) compared to WT mice. T = thickness. *P < 0.05; **P < 0.01; ***P < 0.001. Data are represented as mean ± standard error of the mean. The data underlying this Figure can be found in S1 Data.