Figure 2. PARP-1 deletion enhances SVZ cell proliferation.

(A–C) P11 mice were sacrificed to assess SVZ proliferation using immunofluorescence labeling for KI67. Four static images of the SVZ were collected and cells in the dorsolateral SVZ counted for each animal. PARP-1 KO mice had significantly more KI67+ cells (B, C, **p<0.01) than WT mice (A, C). (D–F) To confirm the effects on SVZ proliferation, mice were injected with BrdU (100 mg/kg, i.p.) 2 hours prior to sacrifice. Immunohistochemistry was performed to identify BrdU-positive cells in the SVZ and stereology performed to obtain a population estimate for the dorsolateral SVZ. PARP-1 KO mice (E) appeared to have significantly more BrdU-positive SVZ cells than WT mice (D), which was confirmed with stereology (F, **p<0.01). Coronal forebrain sections were immunostained with an antibody to CD-133 (prominin-1) to identify ependymal cells that may act as neural stem cells. Sections were double-stained with an antibody to BrdU to determine if CD133+ cells in the lateral ventricle are actively proliferating. Very few CD133+ cells were labeled along the lateral ventricle in P11 WT mice (G) and were generally found at the posterior striatal level, just before the appearance of the hippocampus. Numerous CD133+ cells were apparent in the PARP-1 KO ependymal layer (H). Quantification confirmed a significant increase in CD133+ cells in PARP-1 KO mice compared with WT mice (I, *p<0.05). All data are shown with SEM. Scale bars: 25 μm in A for A–B; 50 μm in D–E; 25 μm in H for G–H.