Amyloid ? Is Not The Major Factor Accounting For Impaired Adult Hippocampal Neurogenesis In Mice Overexpressing Amyloid Precursor Protein

New neurons were generated continuously in the dentate gyrus(DG)of hippocampus throughout adulthood in rodents and most other mammals.Newly generated neurons could be integrated into the preexisting neural circuits and were associated with learning and memory and other cognitive functions such as mood regulation.Previous studies showed that adult hippocampal neurogenesis was impaired in several lines of animal models of Alzheimer's disease(AD).These animal models expressed much higher levels of both amyloid ?(A?)and APP compared with nontransgenic control mice.Therefore,it was unclear whether the impaired adult hippocampal neurogenesis was caused by high levels of A? or APP.In the present study,we firstly investigated the adult hippocampal neurogenesis in hAPP-I5 mice,and then compared it with that in hAPP-J20 mice by BrdU labeling combined with retrovirus-GFP injection and reporter lines including POMC-GFP and Nestin-GFP mice,we found that the mature adult-born neurons labeled by BrdU and NeuN,2-3-week-old DCX-positive immature neurons and dividing cells labeled by BrdU and MCM2 in hAPP-I5 mice were all significantly less than those in nontransgenic mice,suggesting that overexpression of wild type hAPP affected adult hippocampal neurogenesis.Meanwhile,we found that the number of mature adult-born new neurons,DCX-positive immature neurons,and proliferating cells in the DG of hAPP-I5 mice was significantly decreased compared with that in hAPP-J20 mice.Subsequently,we confirmed these results by crossing hAPP-I5 and hAPP-J20 mice with POMC-GFP and Nestin-GFP mice,respectively.These data indicated that the decrease degree of adult hippocampal neurogenesis was more prominent in hAPP-I5 mice than that in hAPP-J20 mice.The level of hAPP mRNA in the brain was comparable between hAPP-I5 and hAPP-J20 mice,but the A? level was much higher in hAPP-J20 than that in hAPP-I5 mice.Our results suggested that A? was not the major factor affecting neurogenesis in the adult hippocampus of APP mice.