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P2‐215: ACETYLATED TAU DISTRIBUTION IN THE HUMAN HIPPOCAMPUS
Author(s) -
Ehrenberg Alexander J.,
Morales Dulce Ovando,
Petersen Cathrine,
Hepker Mackenzie,
Li Alissa Nana,
Cosme Celica Glenn,
Miller Bruce L.,
Gan Li,
Seeley William W.,
Grinberg Lea Tenenholz
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.903
Subject(s) - hippocampal formation , subiculum , hippocampus , entorhinal cortex , chemistry , pathology , dentate gyrus , senile plaques , tau protein , alzheimer's disease , neuroscience , biology , medicine , disease
utilized for the prevention of memory loss or restoration of lost memories. In our study we investigated how production of new hippocampal neurons changes with age.Methods: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 themouse brain were labeled by a single intraperitoneal injection of 5-Ethynyl-20-deoxyuridine. Mouse brains were processed, stained for EdU, and coordinate of all proliferating cells were obtained and represented as a point cloud. Results: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 2months and 2.5 years. We propose a model that mechanistically explains changes in neurogenesis with age and also discuss possible implications of this new model on the development of new therapies based on the induction of neurogenesis in the SGZ. Conclusions: 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.