Document Detail

Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone.
MedLine Citation:
PMID:  21948688     Owner:  NLM     Status:  MEDLINE    
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.
Elizabeth A Stoll; Behnum A Habibi; Andrei M Mikheev; Jurate Lasiene; Susan C Massey; Kristin R Swanson; Robert C Rostomily; Philip J Horner
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  29     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2012-03-12     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2005-17     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 AlphaMed Press.
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MeSH Terms
Aging / physiology*
Cell Aging*
Cell Cycle*
Cell Differentiation
Cell Proliferation
Cell Survival
Mice, Inbred C57BL
Mitotic Index
Models, Neurological
Neural Stem Cells / cytology,  physiology
Primary Cell Culture
Prosencephalon / cytology*,  physiology
Staining and Labeling
Time Factors
Time-Lapse Imaging
Grant Support
AG029406/AG/NIA NIH HHS; HDO7183-28//PHS HHS; NSO46724//PHS HHS; R21 AG029406/AG/NIA NIH HHS; R21 AG038305/AG/NIA NIH HHS; T32 HD007183/HD/NICHD NIH HHS

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