Abrogation of Early Apoptosis Does Not Alter Late Inhibition of Hippocampal Neurogenesis After Irradiation

Journal Article · Thu Jul 15 04:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

OSTI ID:21451139

Yuqing, Li ^[1]; Aubert, Isabelle ^[2]

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1. Cancer, Sunnybrook Health Sciences Centre, Toronto (Canada)
2. Brain Sciences Research, Sunnybrook Health Sciences Centre, Toronto (Canada)

Purpose: Irradiation of the adult brain results in acute apoptosis of neural progenitors and vascular endothelial cells, as well as late dysfunction of neural progenitors and inhibition of neurogenesis. We sought to determine whether the early apoptotic response has a causative role in late inhibition of neurogenesis after cranial irradiation. Methods and Materials: Using a genetic approach with p53 and smpd1 transgenic mice and a pharmacologic approach with basic fibroblast growth factor (bFGF) to abrogate the early apoptotic response, we evaluated the late inhibition of neurogenesis in the hippocampal dentate gyrus after cranial irradiation. Results: In dentate gyrus, subgranular neural progenitors underwent p53-dependent apoptosis within 24 h after irradiation. Despite a near abrogation of neural progenitor apoptosis in p53-/- mice, the reduction in newborn neurons in dentate gyrus at 9 weeks after irradiation in p53-/- mice was not different from that observed in wildtype controls. Endothelial cell apoptosis after radiation is mediated by membrane damage initiated by activation of acid sphingomyelinase (ASMase). Deletion of the smpd1 gene (which encodes ASMase) attenuated the apoptotic response of endothelial cells. At 9 weeks after irradiation, the inhibition of hippocampal neurogenesis was not rescued by ASMase deficiency. Intravenous administration of bFGF protected both endothelial cells and neural progenitors against radiation-induced apoptosis. There was no protection against inhibition of neurogenesis at 9 weeks after irradiation in bFGF-treated mice. Conclusion: Early apoptotic death of neural progenitors, endothelial cells, or both does not have a causative association with late inhibition of neurogenesis after irradiation.

• OSTI ID: 21451139
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 4 Vol. 77; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANIMALS
APOPTOSIS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
CONNECTIVE TISSUE CELLS
FIBROBLASTS
GROWTH FACTORS
INHIBITION
IRRADIATION
MAMMALS
MICE
MITOGENS
NERVE CELLS
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RODENTS
SOMATIC CELLS
TRANSGENIC ANIMALS
TRANSGENIC MICE
VERTEBRATES