Villasana L, Poage C, van Meer P, Raber J
Department of Behavioral Neuroscience, ONPRC, Oregon Health and Science University, Portland, Oregon 97239, USA.
Radiats Biol Radioecol. 2008 Mar-Apr;48(2):167-70.
Cranial irradiation is associated with long-term cognitive impairments, including deficits in hippocampus-dependent learning and memory. Not all people exposed to cranial radiation develop cognitive injury, suggesting the involvement of genetic risk factors. There may also be sex differences in susceptibility to develop radiation-induced cognitive injury. The three major human apolipoprotein E (apoE) isoforms are encoded by distinct alleles (epsilon2, epsilon3, and epsilon4). Compared with epsilon3, epsilon4 increases the risk of cognitive impairments following various challenges while epsilon2 provides relative protection. Women are at higher risk to develop Alzheimer's disease (AD) than men, particularly those carrying epsilon4. In previous experiments using male and female mice expressing human apoE-isoforms E2, E3 or E4 under the mouse apoE promoter, we showed that cranial irradiation with 137Cs (10 Gy) results in hippocampus-dependent cognitive impairments that are sex- and apoE-isoform dependent. 137Cs is a form of irradiation often used in the clinical setting. To investigate whether 56Fe irradiation also has sex- and apoE-isoform dependent effects on hippocampus-dependent cognitive function in human apoE mice, we sham-irradiated and irradiated 2-month old male and female human apoE mice at 3 Gy and assessed their performance in a passive avoidance learning and memory test three to five months later.
颅脑照射与长期认知障碍有关，包括海马体依赖的学习和记忆缺陷。并非所有接受颅脑照射的人都会发生认知损伤，这表明遗传风险因素也参与其中。在发生辐射诱导的认知损伤易感性方面可能也存在性别差异。人类载脂蛋白E（apoE）的三种主要异构体由不同的等位基因（ε2、ε3和ε4）编码。与ε3相比，ε4在面临各种挑战后会增加认知障碍的风险，而ε2则提供相对保护。女性患阿尔茨海默病（AD）的风险高于男性，尤其是携带ε4的女性。在之前的实验中，我们让雄性和雌性小鼠在小鼠apoE启动子的作用下表达人类apoE异构体E2、E3或E4，结果显示，137Cs（10 Gy）颅脑照射会导致海马体依赖的认知障碍，且这种障碍具有性别和apoE异构体依赖性。137Cs是临床环境中常用的一种照射形式。为了研究56Fe照射对人类apoE小鼠海马体依赖的认知功能是否也有性别和apoE异构体依赖性影响，我们对2月龄的雄性和雌性人类apoE小鼠进行了假照射和3 Gy的照射，并在三到五个月后评估它们在被动回避学习和记忆测试中的表现。
