title: Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia.
abstract: 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.
authors.affiliation: Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945-0638, USA.
authors.forename: Huidong
authors.initials: H
authors.lastname: Tang
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: XiaoOu
authors.initials: X
authors.lastname: Mao
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Won
authors.forename: Veronica
authors.initials: V
authors.lastname: Galvan
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
mesh_terms: 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*