Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone

Elizabeth A. Stoll, Behnum A. Habibi, Andrei M. Mikheev, Jurate Lasiene, Susan C. Massey, Kristin Swanson, Robert C. Rostomily, Philip J. Horner

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2005-2017
Number of pages13
JournalStem Cells
Volume29
Issue number12
DOIs
StatePublished - Dec 2011
Externally publishedYes

Fingerprint

Lateral Ventricles
Cell Cycle
Stem Cells
Time-Lapse Imaging
Neurons
Neurogenesis
Prosencephalon
Synapses
Thymidine
Young Adult
Cell Death
Theoretical Models
Brain
Growth

Keywords

  • Aging
  • Mitotic activity
  • Mitotic rate
  • Neurogenesis
  • Progenitor
  • Survival

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Stoll, E. A., Habibi, B. A., Mikheev, A. M., Lasiene, J., Massey, S. C., Swanson, K., ... Horner, P. J. (2011). Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone. Stem Cells, 29(12), 2005-2017. https://doi.org/10.1002/stem.747

Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone. / Stoll, Elizabeth A.; Habibi, Behnum A.; Mikheev, Andrei M.; Lasiene, Jurate; Massey, Susan C.; Swanson, Kristin; Rostomily, Robert C.; Horner, Philip J.

In: Stem Cells, Vol. 29, No. 12, 12.2011, p. 2005-2017.

Research output: Contribution to journalArticle

Stoll, EA, Habibi, BA, Mikheev, AM, Lasiene, J, Massey, SC, Swanson, K, Rostomily, RC & Horner, PJ 2011, 'Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone', Stem Cells, vol. 29, no. 12, pp. 2005-2017. https://doi.org/10.1002/stem.747
Stoll, Elizabeth A. ; Habibi, Behnum A. ; Mikheev, Andrei M. ; Lasiene, Jurate ; Massey, Susan C. ; Swanson, Kristin ; Rostomily, Robert C. ; Horner, Philip J. / Increased re-entry into cell cycle mitigates age-related neurogenic decline in the murine subventricular zone. In: Stem Cells. 2011 ; Vol. 29, No. 12. pp. 2005-2017.
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