Abstract:
:Therapeutic irradiation of the brain can cause a progressive cognitive dysfunction that may involve defects in neurogenesis. In an effort to understand the mechanisms underlying radiation-induced stem cell dysfunction, neural precursor cells isolated from the adult rat hippocampus were analyzed for acute (0-24 h) and chronic (3-33 days) changes in apoptosis and reactive oxygen species (ROS) after exposure to X rays. Irradiated neural precursor cells exhibited an acute dose-dependent apoptosis accompanied by an increase in ROS that persisted over a 3-4-week period. The radiation effects included the activation of cell cycle checkpoints that were associated with increased Trp53 phosphorylation and Trp53 and p21 (Cdkn1a) protein levels. In vivo, neural precursor cells within the hippocampal dentate subgranular zone exhibited significant sensitivity to radiation. Proliferating precursor cells and their progeny (i.e. immature neurons) exhibited dose-dependent reductions in cell number. These reductions were less severe in Trp53-null mice, possibly due to the disruption of apoptosis. These data suggest that the apoptotic and ROS responses may be tied to Trp53-dependent regulation of cell cycle control and stress-activated pathways. The temporal coincidence between in vitro and in vivo measurements of apoptosis suggests that oxidative stress may provide a mechanistic explanation for radiation-induced inhibition of neurogenesis in the development of cognitive impairment.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Limoli CL,Giedzinski E,Rola R,Otsuka S,Palmer TD,Fike JRdoi
10.1667/rr3112subject
Has Abstractpub_date
2004-01-01 00:00:00pages
17-27issue
1eissn
0033-7587issn
1938-5404pii
RR3112journal_volume
161pub_type
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journal_title:Radiation research
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journal_title:Radiation research
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journal_title:Radiation research
pub_type: 杂志文章
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1984-12-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
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journal_title:Radiation research
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1999-03-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
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journal_title:Radiation research
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:1990-10-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
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更新日期:1998-05-01 00:00:00
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journal_title:Radiation research
pub_type: 杂志文章
doi:
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journal_title:Radiation research
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