Effects of age and strain on cell proliferation in the mouse rostral migratory stream.
The number of neural progenitor cells (NPCs) decreases with advancing age, and the mechanisms responsible for this decline is unclear. Here, we demonstrate the importance of genetics as a modulator for the age-related decline in NPCs. We systematically quantified the number of proliferating NPCs in the rostral migratory stream, the rostral extension of the subventricular zone, in 9 inbred mouse strains from 3 to 18 months of age. A striking negative impact of age and significant interstrain differences in the number of NPCs was detected at 3 and 12 months of age. Extended proliferative profiles of C57BL/6J and DBA/2J from 3 to 24 months of age revealed differential dynamics of the age-related decline in NPCs. Statistically significant interaction effects for age and strain were detected over the 3- to 7-month period. Strain differences were mapped to several genetic loci suggesting complex genetic control of NPC proliferation at different ages. Furthermore, correlational analyses revealed the differential regulation of cell proliferation and genes that may underlie the proliferative deficits of NPCs in the aging brain.
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Anna
A
Poon
Dan
D
Goldowitz
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000502:physiology*; D005260:Female; D020547:Lateral Ventricles / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D058953:Neural Stem Cells / Q000166:cytology*; D013045:Species Specificity