2010年10月
Apoptosis-inducing factor deficiency decreases the proliferation rate and protects the subventricular zone against ionizing radiation
CELL DEATH & DISEASE
- 巻
- 1
- 号
- 開始ページ
- 10
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/cddis.2010.63
- 出版者・発行元
- NATURE PUBLISHING GROUP
Cranial radiotherapy in children often leads to progressive cognitive decline. We have established a rodent model of irradiation-induced injury to the young brain. A single dose of 8 Gy was administered to the left hemisphere of postnatal day 10 (P10) mice. Harlequin (Hq) mice, carrying the hypomorphic apoptosis-inducing factor AIF(Hq) mutation, express 60% less AIF at P10 and displayed significantly fewer dying cells in the subventricular zone (SVZ) 6 h after IR, compared with wild type (Wt) littermates. Irradiated cyclophilin A-deficient (CypA(-/-)) mice confirmed that CypA has an essential role in AIF-induced apoptosis after IR. Hq mice displayed no reduction in SVZ size 7 days after IR, whereas 48% of the SVZ was lost in Wt mice. The proliferation rate was lower in the SVZ of Hq mice. Cultured neural precursor cells from the SVZ of Hq mice displayed a slower proliferation rate and were more resistant to IR. IR preferentially kills proliferating cells, and the slower proliferation rate in the SVZ of Hq mice may, at least partly, explain the protective effect of the Hq mutation. Together, these results indicate that targeting AIF may provide a fruitful strategy for protection of normal brain tissue against the detrimental side effects of IR. Cell Death and Disease (2010) 1, e84; doi: 10.1038/cddis.2010.63; published online 21 October 2010
- リンク情報
- ID情報
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- DOI : 10.1038/cddis.2010.63
- ISSN : 2041-4889
- ORCIDのPut Code : 45519532
- Web of Science ID : WOS:000283582100006