Figure 3. Astrocytic CREB regulation in NAc of susceptible mice.
A–B) Representative IHC images for total (A) and pCREB (B) in astrocytes (SOX9, blue) and neurons (NEUN, green) from the core (left) and shell (right) of NAc after CSDS. Across the C) entire NAc, total CREB expression is decreased in Sus astrocytes compared to Res and Ctrl astrocytes (F(2,337) = 6.538, P = 0.0016; Tukey post-hoc *p = 0.0227; **p = 0.0019), with no difference between Ctrl and Res astrocytes (Tukey post-hoc p = 0.8360). Similar effects were observed in the D) core (F(2,235) = 9.976, P = 0.0002; Tukey post-hoc *p = 0.027; ***p < 0.001) and E) shell F(2,248) = 6.659, P = 0.0015; Tukey post-hoc **p = 0.0157; ***p = 0.002). F) Pearson r correlation of individual animal’s mean total astrocytic CREB expression and Interaction Ratio (SI score) reveals a strong positive correlation (r(12) = 0.649, p = 0.022, R2 = 0.422). G) In contrast, increased expression of the canonical activated form of CREB (pCREB) was observed in Sus compared to Ctrl and Res astrocytes (F(2,285) = 26.72, P < 0.0001; Tukey post-hoc ****p < 0.0001), with no difference between Res and Ctrl astrocytes (Tukey post-hoc p = 0.109). This increase in pCREB in Sus astrocytes was observed in H) NAc core (F(2,178) = 23.49, P < 0.0011; Tukey post-hoc ***p = 0.027; ****p < 0.001). However, within the shell, increased pCREB in Sus was only observed compared to Ctrl and not Res astrocytes (F(2,150) = 3.760, P = 0.0255; Tukey post-hoc *p = 0.034). J) Pearson r correlation of individual animal’s mean astrocytic pCREB expression and Interaction Ratio (SI score) reveals a negative correlation (r(12) = −0.762, p = 0.004, R2 = 0.579). Data represented as mean +/− SEM; n = 5 mice per condition. pCREB: phosphorylated CREB; NAc: nucleus accumbens; CSDS: chronic social defeat stress; Res: resilient; Sus: susceptible; Ctrl: control.