a cell autonomous fashion in the adult brain (Ge et al., 2006). Immunostaining of pAKT and DCX, an immature neuronal marker, showed a significant increase of pAKT in GFP+DCX+ new neurons expressing DISC1-shRNA, but not control-shRNA, at 14 days post viral injection (dpi) in comparison to unlabeled GFP-DCX+ new neurons in the same preparation (Figures 1A and 1B). Time-course analysis further showed that the increase of pAKT level was initiated after 7 dpi (Figure 1B), a time when almost all GFP+ cells became post-mitotic (Ge et al., 2006). S6 is a well-characterized downstream target of AKT-mTOR pathway and phosphorylation of S6 (pS6 at Ser235/236) has been commonly used as an indicator for the activation of AKT signaling (Manning and Cantley, 2007). Similar time course of pS6 elevation was found in GFP+DCX+ neurons expressing DISC1-shRNA in comparison to GFP+DCX+ new neurons expressing control-shRNA or uninfected GFP-DCX+ neurons in the same section (Figures 1C and 1D). Taken together, these results suggest that AKT signaling is tightly controlled and DISC1 may be essential in maintaining AKT signaling at low levels in newborn neurons in the adult brain.
