Fig. 2

Activated microglia and astroglia in the brain of mice expressing the Plcγ2-P522R protective mutation. a Volcano blot showing significantly (p < 0.05 y-axis, dotted line) down- and upregulated genes and their log2-transformed fold-changes (x-axis) in the brain of Plcγ2-P522R homozygous knock-in (KI) mice as compared to the wild type (WT) littermates, n = 3 per genotype. b Heatmap showing pathway scores for neuropathology panel-derived pathway annotations. Significantly changed pathways are indicated with asterisk, n = 3 per genotype, Independent samples t-test, *p < 0.05, **p < 0.01, ***p < 0.001. c Representative images (left) of Iba1, P2ry12, and Gfap-stained cortex or hippocampus from WT and KI mice. Quantitation (right) of Iba1-positive microglia, microglia morphology, P2ry12, and Gfap levels. Scale bars represent 10 μm and 5 μm (box in the right corner). Mean ± SD, n = 4 per genotype, two-tailed unpaired t-test, *p < 0.05. D) Immunoblot showing phosphorylation status and total levels of Mapk/Erk and Akt in the total brain lysates of the WT and KI mice. Quantitation showing activity-related phosphorylation of Y204 and S473/474 epitopes in Mapk1/Erk2 and Akt (pan-antibody for Akt1 and Akt2), respectively, normalized to the respective total protein levels. Total protein levels are normalized to that of Gapdh within the same sample. Mean ± SD, % of WT, n = 3–4 per genotype. Independent samples t-test, *p < 0.05