Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia.
The observed age-related decline in neurogenesis may result from reduced proliferation or increased death rate of neuronal precursor cells (NPCs). We found that caspase-3, but not caspase-6, -7, or -9, was activated in NPCs in neurogenic regions of young, young-adult, middle-aged and aged rat brains. The number of capase-3-immunoreactive cells was highest in young and lowest in aged rats. Surprisingly, intraventricular administration of a caspase-3 inhibitor failed to restore the number of BrdU-positive cells in the aged dentate gyrus, suggesting that the age-related decline in neurogenesis may be attributable primarily to reduced proliferation. Additionally, we also found that NPCs in the subventricular zone of young-adult and aged rat brain were increased after focal cerebral ischemia, suggesting that the increase in neurogenesis induced by ischemia may result from an increase in the rate of NPC proliferation, but not from a decrease in NPC death. Thus, our results suggest that age-related and injury-induced changes in the rate of neurogenesis are controlled at the level of NPC proliferation. Furthermore, our results may imply that the mechanisms that maintain a stable population of NPCs in the normal adult and in the ischemic brain, which account for the observed age-dependent reduction or injury-induced increases in neurogenesis, impinge on the regulation of cell division at the NPC level.
Tang
Huidong
H
Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945-0638, USA.
Wang
Yaoming
Y
Xie
Lin
L
Mao
XiaoOu
X
Won
Seok Joon
SJ
Galvan
Veronica
V
Jin
Kunlin
K
D000375:Aging / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology*; D049109:Cell Proliferation; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000473:pathology*