Open AccessIncreased Re‐Entry into Cell Cycle Mitigates Age‐Related Neurogenic Decline in the Murine Subventricular Zone
Author(s) -
Stoll Elizabeth A.,
Habibi Behnum A.,
Mikheev Andrei M.,
Lasiene Jurate,
Massey Susan C.,
Swanson Kristin R.,
Rostomily Robert C.,
Horner Philip J.
Publication year - 2011
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.747
Subject(s) - subventricular zone , biology , neurogenesis , progenitor cell , microbiology and biotechnology , neural stem cell , mitosis , cell cycle , precursor cell , stem cell , in vivo , forebrain , cell , neuroscience , central nervous system , genetics
Although new neurons are produced in the subventricular zone (SVZ) of the adult mammalian brain, fewer functional neurons are produced with increasing age. The age‐related decline in neurogenesis has been attributed to a decreased pool of neural progenitor cells (NPCs), an increased rate of cell death, and an inability to undergo neuronal differentiation and develop functional synapses. The time between mitotic events has also been hypothesized to increase with age, but this has not been directly investigated. Studying primary‐cultured NPCs from the young adult and aged mouse forebrain, we observe that fewer aged cells are dividing at a given time; however, the mitotic cells in aged cultures divide more frequently than mitotic cells in young cultures during a 48‐hour period of live‐cell time‐lapse imaging. Double‐thymidine‐analog labeling also demonstrates that fewer aged cells are dividing at a given time, but those that do divide are significantly more likely to re‐enter the cell cycle within a day, both in vitro and in vivo. Meanwhile, we observed that cellular survival is impaired in aged cultures. Using our live‐cell imaging data, we developed a mathematical model describing cell cycle kinetics to predict the growth curves of cells over time in vitro and the labeling index over time in vivo. Together, these data surprisingly suggest that progenitor cells remaining in the aged SVZ are highly proliferative. S TEM C ELLS 2011;29:2005–2017.