Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis
Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis
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DOI：
10.1667/rr3206
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发表时间：
2004-07-01
影响因子：
3.4
通讯作者：
Fike, JR
中科院分区：
文献类型：
--
作者：
Raber, J;Rola, R;Fike, JR
在治疗脑肿瘤、某些头颈部肿瘤和其他疾病（如动静脉畸形）的过程中，正常大脑暴露于电离辐射。虽然高辐射剂量可导致严重的组织破坏，但较低剂量可引起认知障碍，而没有明显的组织损伤迹象。这些损伤的潜在发病机制还不清楚，但可能涉及海马齿状回的神经前体细胞。为了评估辐射对认知功能的影响，2个月大的小鼠接受假治疗（对照）或海马/皮质局部X射线照射（10戈伊），并在3个月后进行行为测试。与对照组相比，X射线照射的小鼠在巴恩斯迷宫中表现出海马依赖性空间学习和记忆障碍，但在Morris水迷宫中没有表现出这种障碍。未检测到非空间学习和记忆障碍。认知障碍与齿状回颗粒下区（SGZ）增殖Ki-67阳性细胞和Doublecortin阳性未成熟神经元的减少有关。这项研究表明，在适度剂量的辐射后，显着的认知障碍，并表明，巴恩斯迷宫是特别敏感的检测辐射诱导的认知缺陷的年轻成年小鼠。增殖的SGZ细胞及其后代的显著损失表明神经发生减少在辐射引起的认知障碍的发病机制中起着促进作用。(C)2004年，辐射研究协会。
During treatment of brain tumors, some head and neck tumors, and other diseases, like arteriovenous malformations, the normal brain is exposed to ionizing radiation. While high radiation doses can cause severe tissue destruction, lower doses can induce cognitive impairments without signs of overt tissue damage. The underlying pathogenesis of these impairments is not well understood but may involve the neural precursor cells in the dentate gyrus of the hippocampus. To assess the effects of radiation on cognitive function, 2-month-old mice received either sham treatment (controls) or localized X irradiation (10 Gy) to the hippocampus/cortex and were tested behaviorally 3 months later. Compared to controls, X-irradiated mice showed hippocampal-dependent spatial learning and memory impairments in the Barnes maze but not the Morris water maze. No nonspatial learning and memory impairments were detected. The cognitive impairments were associated with reductions in proliferating Ki-67-positive cells and Doublecortin-positive immature neurons in the subgranular zone (SGZ) of the dentate gyrus. This study shows significant cognitive impairments after a modest dose of radiation and demonstrates that the Barnes maze is particularly sensitive for the detection of radiation-induced cognitive deficits in young adult mice. The significant loss of proliferating SGZ cells and their progeny suggests a contributory role of reduced neurogenesis in the pathogenesis of radiation-induced cognitive impairments. (C) 2004 by Radiation Research Society.