The Role Of Autophagy In The Control Of Neurogenesis In The Dentate Gyrus After Hippocampal Lesion

Objective: To investigate the relationship between the survival of the newborn cells in the dentate gyrus after hippocampal lesion and the activation of autophagy in adult rats, and to observe the relationship between the neurogenesis in the dentate gyrus and the ability of learning and memory.Methods: Unilateral hippocampal lesion was established by intrahippocampal microinjection of kainic acid into CA1 subfield. 5-Bromodeoxyuridine(BrdU) was used to mark the proliferating cells, the BrdU-positive cells in the dentate gyrus at different time points were identified by immunohistochemistry and the number of BrdU-positive cells was estimated by stereological method. LC3, Beclin 1 and apoptosis-related protein Bcl-2 were detected with western blot, double-staining of autophagy-spicific marker LC3, Beclin 1and BrdU was performed;which were used to observe the role of autophagy in the reduction of newborn cells. Y maze performmance was used to estimate the relationship between the newborn cell survival and the ability of learning and memory.Results: Quantitative analysis of BrdU-labeling revealed that as compared with the control group, the experimental group had the most positive cells in DG on the first day after 3 day administration of BrdU. The number of BrdU-positive cells in experimental group reduced gradually. Western blot analysis revealed that as compared with the control groups, the experimental groups'expression of LC3 and Beclin 1 were up-regulated and the expression of Bcl-2 were down-regulated . BrdU/LC3, BrdU/Beclin 1 double-labelled cells were not found on each time point after hippocampal damage. The performance of Y maze of experimental groups was deteriorated as compared with the control groups, but ameliorated with time. One month after lesion, the difference between the sham and the experimental groups was not significant.Conclusion: Hippocampal damage in adult rats can enhance the neurogensis in DG, which reduced progressively with time, the autophagic cell death may take part in the reduction of newborn cells. The survival of newborn cells plays a role on the resumption of learning and memory capacity.