Department of Radiation Medicine, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
Radiat Res. 2010 Mar;173(3):342-52. doi: 10.1667/RR1825.1.
Abstract An unavoidable complication of space travel is exposure to high-charge, high-energy (HZE) particles. In animal studies, exposure of the CNS to HZE-particle radiation leads to neurological alterations similar to those seen in aging or Alzheimer's disease. In this study we examined whether HZE-particle radiation accelerated the age-related neuronal dysfunction that was previously described in transgenic mice overexpressing human amyloid precursor protein (APP). These APP23 transgenic mice exhibit age-related behavioral abnormalities and deficits in synaptic transmission. We exposed 7-week-old APP23 transgenic males to brain-only (56)Fe-particle radiation (600 MeV/nucleon; 1, 2, 4 Gy) and recorded synaptic transmission in hippocampal slices at 2, 6, 9, 14 and 18-24 months. We stimulated Schaeffer collaterals and recorded field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) in CA1 neurons. Radiation accelerated the onset of age-related fEPSP decrements recorded at the PS threshold from 14 months of age to 9 months and reduced synaptic efficacy. At 9 months, radiation also reduced PS amplitudes. At 6 months, we observed a temporary deficit in paired-pulse inhibition of the PS at 2 Gy. Radiation did not significantly affect survival of APP23 transgenic mice. We conclude that irradiation of the brain with HZE particles accelerates Alzheimer's disease-related neurological deficits.
太空旅行不可避免的会产生暴露于高电荷、高能量（HZE）粒子的并发症。在动物研究中，中枢神经系统暴露于 HZE 粒子辐射会导致与衰老或阿尔茨海默病相似的神经改变。在这项研究中，我们研究了 HZE 粒子辐射是否会加速之前在过表达人淀粉样前体蛋白（APP）的转基因小鼠中描述的与年龄相关的神经元功能障碍。这些 APP23 转基因小鼠表现出与年龄相关的行为异常和突触传递缺陷。我们用 7 周龄 APP23 转基因雄性小鼠进行脑照射（56）Fe 粒子辐射（600 MeV/nucleon；1、2、4 Gy），并在 2、6、9、14 和 18-24 个月时记录海马切片中的突触传递。我们刺激 Schaeffer 侧支，记录 CA1 神经元中的场兴奋性突触后电位（fEPSP）和群体锋电位（PS）。辐射加速了从 14 个月到 9 个月记录到的与年龄相关的 PS 阈值下 fEPSP 下降的发生，并降低了突触效能。在 9 个月时，辐射还降低了 PS 幅度。在 6 个月时，我们观察到在 2 Gy 时 PS 的成对脉冲抑制出现暂时缺陷。辐射对 APP23 转基因小鼠的存活率没有显著影响。我们得出结论，用 HZE 粒子照射大脑会加速与阿尔茨海默病相关的神经缺陷。
