BACKGROUND:Abnormal hippocampal neurogenesis during aging has been reported to result in learning and memory dysfunction. But its mechanism is unclear.
OBJECTIVE: To understand the changes of mouse neurogenesis in the hippocampal subgranular zone during aging.
METHODS:C57BL/6 mice 2, 6 and 20 months of age were used. Immunochemistry was used to count the number of neural stem cels (nestin+), neuroblasts (Doublecortin+, DCX+), and proliferative cels (proliferating cel nuclear antigen+, PCNA+) in the hippocampal subgranular zone. mRNA expressions of aging-related genes, p19Arf and p21Cip1/Waf1, in the hippocampus were detected by reverse transcription-PCR.
RESULTS AND CONCLUSION: Compared with the young and middle age groups, the number of PCNA+ cels, nestin+ and DCX+ cels in the hippocampal subgranular zone of the aged group decreased dramaticaly; the expression of p19Arf and p21Cip1/Waf1 mRNA increased in the aged group. Proliferation activity, the number of neural stem cels and neuronal differentiation al decreased. These findings indicate that the decline of hippocampal neurogenesis may be associated with increased expression of aging-related genes p19Arf and p21Cip1/Waf1 in the p19Arf-Mdm2-p53-p21Cip1/Waf1pathway.