Chunk #24 — RESULTS — Rescue of developmental defects of new neurons from DISC1 knockdown and KIAA1212 overexpression by pharmacological inhibition of mTOR, but not by inhibition of GSK3β
We also examined the potential role of GSK3β in DISC1-dependent regulation of new neuron development. A recent study showed that pharmacological inhibition of GSK3β by SB-216763 normalized the decreased proliferation of adult neural progenitors from lentivirus-mediated expression of DISC1-shRNA in the adult dentate gyrus (Mao et al., 2009). We focused our study on the neuronal developmental stage of newborn dentate granule cells beyond the proliferation stage. After daily application of SB-216763 for 14 days, GFP+ neurons expressing DISC1-shRNA or KIAA1212 still exhibited significant developmental defects, including soma hypertrophy, ectopic dendrites and increased dendritic length and complexity (Figure S8). There was a moderate increase in the number of BrdU labeled cells examined at 2 hrs after BrdU injection on 14 dpi (data not shown), suggesting an increased proliferation of adult neural progenitors in the dentate gyrus.
