The Role Of Apoptosis In The Regulation Of Cell Proliferation In Dentate Gyrus After Hippocampal Lesion

Objective:To investigate the mechanism of the reduction of newborn cells and the effect of newborn cells on the ability of learning and memory in the dentate gyrus (DG) after hippocampus CA1 lesion in adult rats.Method: Adult rats were used to establish hippocampus lesion by intrahippocampal microinjection of kainic acid; 5-Bromodeoxyuridine(BrdU) was used to label the proliferating cells; the BrdU-positive cells in DG after hippocampal lesion were identified by immunohistochemistry at various time points and the number of BrdU-positive cells in DG was estimated by stereological method; the co-expression of BrdU and cleaved caspase-3 was observed using the laser confocal fluorescence microscopy; apoptosis related protein levels of caspase-3 and p53 were detected with Western Blot analysis; Y maze training was conducted to evaluate the ability of learning and memory.Results: Immunohistochemical quantitative analysis revealed that comparing with that of control, the experimental group had obvious more BrdU-positive cells in DG at each time point after hippocampal lesion; Each group had the most BrdU-positive cells on the first day after administration of BrdU and gradually reduced with time; There were few BrdU/cleaved caspase-3 double-labelled cells both in the granular cell zone and the hilus. Western Blot analysis demonstrated the decrease in pro-caspase-3 and the increase in p53 protein levels in experimental group. Y maze performance were tested at 6~8, 18~20 or 25~27 days after BrdU injection. At 6~8 and 18~20 days after BrdU injection, EN(error number) of the experimental group was significantly more than that of control, however, the difference was no longer apparent at 25~27 days after BrdU injection between the two groups.Conclusion: The total number of the proliferating cells in DG reduced with time after hippocampal lesion in adult rats, one of its mechanisms might be related to apoptosis; the impairment of the ability of learning and memory after hippocampal lesion could recover in some degree.