Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain.
The adult mammalian brain retains the capacity for neurogenesis, by which new neurons may be generated to replace those lost through physiological or pathological processes. However, neurogenesis diminishes with aging, and this casts doubt on its feasibility as a therapeutic target for cell replacement therapy in stroke and neurodegenerative disorders, which disproportionately affect the aged brain. In previous studies, neurogenesis was stimulated by cerebral ischemia in young rodents, and the neurogenesis response of the aged rodent brain to physiological stimuli, such as hormonal manipulation and growth factors, was preserved. To investigate the effect of aging on ischemia-induced neurogenesis, transient (60 min) middle cerebral artery occlusion was induced in young adult (3-month) and aged (24-month) rats, who were also given bromodeoxyuridine to label newborn cells. As found in prior studies, basal neurogenesis in control, nonischemic rats was reduced with aging. Ischemia failed to stimulate neurogenesis in the dentate gyrus (DG) subgranular zone (SGZ), in contrast to results obtained previously after more prolonged (90-120 min) middle cerebral artery occlusion, but increased the number of BrdU-labeled cells in the forebrain subventricular zone (SVZ). This effect was less prominent in aged than in young adult rats, with fold-stimulation of BrdU incorporation reduced by approximately 20% and the total number of cells generated diminished by approximately 50%. BrdU-labeled cells in SVZ coexpressed neuronal lineage markers, consistent with newborn neurons. We conclude that ischemia-induced neurogenesis occurs in the aged brain, and that measures designed to augment this phenomenon might have therapeutic applications.
Jin
Kunlin
K
Buck Institute for Age Research, Novato, CA 94945, USA.
Minami
Manabu
M
Xie
Lin
L
Sun
Yunjuan
Y
Mao
Xiao Ou
XO
Wang
Yaoming
Y
Simon
Roger P
RP
Greenberg
David A
DA
D000375:Aging; D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D018891:Dentate Gyrus / Q000473:pathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D020547:Lateral Ventricles / Q000473:pathology; D008297:Male; D009474:Neurons / Q000473:pathology* / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344
D001973:Bromodeoxyuridine