Seizure evolution in a mouse model of West syndrome involves complex and time-dependent synapse remodeling, gliosis and alterations in lipid metabolism
Fig 8
Proteomic and lipidomic changes in the hippocampus of Cyfip2+/R87C mice.
(A) Principal component analysis (PCA) score plots show distinct separations in the proteome between WT and Cyfip2+/R87C mice at PWK 14 and 28. (B) Heatmaps display 3,102 and 3,748 differentially expressed proteins (DEPs) in the hippocampus of Cyfip2+/R87C mice at PWK 14 and 28, respectively. (C) Graphs depict the abundance of Apod and Ptgds proteins in WT and Cyfip2+/R87C mice (n = 8 mice per genotype, Welch’s t test). KI, knock-in. (D) Heatmap illustrates the separation of four distinct protein groups in the proteome of WT and Cyfip2+/R87C mice, categorized based on age-dependent relative abundance differences between the genotypes. (E) GO analysis of proteins in groups B and D (left panel). Protein–protein interaction (PPI) networks for group D proteins, highlighting their associated metabolic processes (right panel). (F) Representative electron microscopy images show astrocytic mitochondria (indicated by red arrows) in the hippocampus of WT and Cyfip2+/R87C mice at PWK 28. (G) PCA score plots display clear separations in the lipidome between WT and Cyfip2+/R87C mice at PWK 14 and 28. (H) A pie chart illustrates the distribution of identified lipid classes in the hippocampus. (I) Pie charts depict the distribution of identified lipid classes across the six groups classified based on the age-dependent relative expression levels in Cyfip2+/R87C mice compared to WT mice. Bar graphs present Z-scores for the four combinations (two ages and two genotypes) across the six groups (n = 9 to 14 mice per genotype, Mann–Whitney test). *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.