p53 is dispensable for apoptosis but controls neurogenesis of mouse dentate gyrus cells following γ-irradiation

Mammalian cells respond to DNA insults by activating cell-cycle checkpoints. This may result in a temporary cell growth arrest which allows DNA repair before proliferation or induces apoptosis. p53 is one of the main contributors in regulating these activities. To get a better insight on the molecular mechanism underlying these activities we studied the role of p53 in apoptosis and neurogenesis of brain cells from adult p53 +/+ or p53 −/− mice exposed to γ-irradiation. Apoptosis and neurogenesis were assessed up to 14 days following the injury. Five–ten hours following γ-irradiation, cells with TUNEL positive nuclei were identified within the subgranular zone of dentate gyrus (DG) of both p53 +/+ and p53 −/− mice. At the same time-points, pyknotic and shrinking nuclei were visualized by Hoechst 33258 staining. Furthermore, γ-irradiation increased the number of proliferating cell nuclear antigen (PCNA) positive cells with a peak at 5–10 h in both animal groups. PCNA immunoreactivity was detected in cells exhibiting condensed nuclei as visualized by Hoechst 33258 staining. Neurogenesis, assessed by mitotic marker p34 cdc2 immunoreactivity, showed a biphasic response to γ-irradiation both in p53 +/+ and p53 −/− mice which was characterized by an early inhibition and a delayed stimulation. In p53 −/− mice, the time required by DG granule cells to recover from the lesion and to stimulate proliferation was significantly shortened in comparison with wild-type mice thus resulting in an accelerated neurogenesis. Our data indicate that following γ-radiation p53 plays a role in regulating cell-cycle progression rate but it is dispensable for promoting apoptosis of DG granule cells.