Next, we investigated which downstream signaling pathways were activated by cell-autonomous activation of ErbB signaling in astrocytes. Because cultured astrocytes differ from in vivo astrocytes [25, 47], we first examined various candidate signaling proteins in brain tissues. Based on WB assays, Akt and Erk, the classic ErbB downstream signaling proteins that are important for astrogliosis, were indeed active in Mlc1-ErbB2V664E cortices (Figure 6a and b). In addition, the classic inflammatory signaling protein, STAT3, which is critical for astrogliosis [10, 13, 48], markedly increased in both level and activity in cortical tissues from Mlc1-ErbB2V664E mice (Figure 6a and b). Moreover, our immunostaining results revealed specific activation and increased levels of STAT3 protein in reactive astrocytes in Mlc1-ErbB2V664E mice (Figure 6c).