Adult neurogenesis occurs throughout life in the subgranular zone (SGZ) of the hippocampal dentate gyrus and the subventricular zone (SVZ) lining the lateral ventricles in the adult mammalian brain. Newborn neurons in SGZ integrate into the neural circuit, thereby implicating in learning and memory. The adult hippocampal neurogenesis is declined with age, however, it still remains unknown about the mechanisms of age-related decline in neurogenesis.
Checkpoint kinase 2 (Chk2), a mediator of DNA damage response, is essential for p53-mediated apoptosis and cell cycle arrest in response to DNA damage. Here we investigated whether Chk2 is involved in the senescence of neural stem cells and the age related-decline of adult neurogenesis in the hippocampus. The weight of the body and brain of 4.5-month-old Chk2 KO mice were indistinguishable from those of wild type mice. Quantitative analysis of the neural stem cells and immature newborn neurons in the whole hippocampi was performed. Unexpectedly, the number of S100beta^-, Sox2⁺ neural stem cells was significantly decreased in the 4.5-month-old Chk2 KO mice compared to that of wild type mice. The number of DCX⁺ immature newborn neurons also was significantly decreased in the Chk2 KO mice. The ratio of immature neurons to neural stem cells of Chk2 KO mice, which indicates the rate of neurogenesis, was comparable to that of wild type mice. This indicated that the decline in neural stem cells led to a decrease in the number of immature newborn neurons in Chk2 KO mice. These results suggest that Chk2 may be required for the maintenance for adult hippocampal neural stem cell pool and cognition during aging.