Fig. 4

Chronic J4 treatment ameliorates the expression of tauopathy associated genes and neurotoxic reactive astrocyte genes in the hippocampi of Tau22 mice. Mice were treated as indicated (WTC, TauC, and TauJ; n = 3 in each group) from the age of 3–10 months. The hippocampus was carefully removed for RNA-seq analysis. Volcano plot of DE genes in the a TauC group vs. WTC group and b TauJ group vs. WTC group. c GO enrichment analysis of DE genes between the TauC and WTC groups (red bar) and TauJ and WTC groups (green bar). d KEGG pathway analysis of DE genes between the TauC and WTC groups (red bar) and TauJ and WTC groups (green bar). e Volcano plot of the DE genes in the TauJ group vs. TauC group. In the volcano plot, the significantly upregulated and downregulated DE genes (absolute log₂ ratio ≥ 0.32; p < 0.05) are shown in red and blue, respectively. f Venn diagram showing the 436 overlapping DE genes between the upregulated DE genes in the TauC group vs. WTC group (pink) and the downregulated DE genes in the TauJ group vs. TauC group (green). g Pie chart of cell-type-enrichment of 436 tauopathy-associated DE genes regulated by J4. In the volcano plot, the significantly upregulated and downregulated DE genes (absolute log₂ ratio ≥ 0.32; p < 0.05) are shown in red and blue, respectively. In the Venn diagram and pie chart, the number and percentage of DE genes in each category were shown in each sector. h, i Heatmap of h DAM genes and i A1-specific genes in the TauC/WTC and TauJ/TauC groups. The relative expression level (log₂ ratio) of genes is shown on a scale from red (upregulated) to blue (downregulated). Asterisks indicate significant alterations (p < 0.05)