Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain

Kunlin Jin, Manabu Minami, Lin Xie, Yunjuan Sun, Xiao Ou Mao, Yaoming Wang, Roger P. Simon, David A. Greenberg

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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 neuro-degenerative 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 ∼20% and the total number of cells generated diminished by ∼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.

Original languageEnglish
Pages (from-to)373-377
Number of pages5
JournalAging Cell
Volume3
Issue number6
DOIs
StatePublished - 1 Dec 2004

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Neurogenesis
Rodentia
Ischemia
Brain
Bromodeoxyuridine
Lateral Ventricles
Middle Cerebral Artery Infarction
Young Adult
Newborn Infant
Physiological Phenomena
Neurons
Dentate Gyrus
Pathologic Processes
Cell- and Tissue-Based Therapy
Prosencephalon
Brain Ischemia
Intercellular Signaling Peptides and Proteins
Cell Count
Stroke
Therapeutics

Keywords

  • Ischemia
  • Nestin
  • Neurogenesis
  • Oligodendrocyte
  • Subgranular zone
  • Subventricular zone

Cite this

Jin, K., Minami, M., Xie, L., Sun, Y., Mao, X. O., Wang, Y., ... Greenberg, D. A. (2004). Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain. Aging Cell, 3(6), 373-377. https://doi.org/10.1111/j.1474-9728.2004.00131.x
Jin, Kunlin ; Minami, Manabu ; Xie, Lin ; Sun, Yunjuan ; Mao, Xiao Ou ; Wang, Yaoming ; Simon, Roger P. ; Greenberg, David A. / Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain. In: Aging Cell. 2004 ; Vol. 3, No. 6. pp. 373-377.
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Jin, K, Minami, M, Xie, L, Sun, Y, Mao, XO, Wang, Y, Simon, RP & Greenberg, DA 2004, 'Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain', Aging Cell, vol. 3, no. 6, pp. 373-377. https://doi.org/10.1111/j.1474-9728.2004.00131.x

Ischemia-induced neurogenesis is preserved but reduced in the aged rodent brain. / Jin, Kunlin; Minami, Manabu; Xie, Lin; Sun, Yunjuan; Mao, Xiao Ou; Wang, Yaoming; Simon, Roger P.; Greenberg, David A.

In: Aging Cell, Vol. 3, No. 6, 01.12.2004, p. 373-377.

Research output: Contribution to journalArticle

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AU - Jin, Kunlin

AU - Minami, Manabu

AU - Xie, Lin

AU - Sun, Yunjuan

AU - Mao, Xiao Ou

AU - Wang, Yaoming

AU - Simon, Roger P.

AU - Greenberg, David A.

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