Description
The Impact of Age on Cell Proliferation in Hippocampal Subgranular Zone in Adult Mouse Brain
Mikhail V. Semënov1,2,*, Karen Smith1
1New England Geriatric Research Education and Clinical Center, Bedford Division, Edith Nourse Rogers Memorial Veterans Hospital, Bedford, Massachusetts, USA; 2Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts, USA
*Corresponding author
The hippocampus is one of the brain areas damaged earlier in the development of Alzheimer's disease. This damage is thought to be linked to memory loss in Alzheimer's patients. The adult brain retains an ability to produce new hippocampal granule neurons. New neurons are thought to be involved in new memory formation, learning, stress response, and emotion. Therefore, the new hippocampal neuron production potentially can be utilized for the prevention of memory loss or restoration of lost memories. In our study, we characterize how the production of neural precursors for new hippocampal neurons changes in the mouse brain relative to age. C57BL/6J male mice were obtained from The Jackson Laboratory (Bar Harbor, ME). The mouse age ranged from 30 days to 2.5 years. Proliferating cells in the mouse brain were labeled by a single intraperitoneal injection of 5-Ethynyl-2´-deoxyuridine. Mouse brains were processed, stained for EdU, and coordinate of all proliferating cells were obtained and represented as a point cloud. We found that production of neural precursors decreases 64 fold from the age of 30 days to the age of 2.5 years. Based on our measurements, we calculated that during this time 1,665,965 new precursors are produced in the subgranular zone (SGZ). The SGZ contains presumptive neural stem cells (NSCs). Using the published estimates of the number of such cells in the SGZ, we calculated that each presumptive NSC on average produces only 33 progenies between the age of 2 months and 2.5 years. We propose a model that mechanistically explains changes in neurogenesis with age. Our model predicts that only treatments which induce neurogenesis by extending the proliferative potential of NSCs or treatments that replenish the NSC population, based for example on the expansion of NSCs poll by promoting symmetrical NSCs division or by introduction of additional NSCs in the SGZ by somatic-stem conversion, should be used.
This study was supported by the Janet and Edward Gilda Charitable Foundation and in part by the Department of Veterans Affairs.