Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity.
Amifostine (WR-2721) Mitigates Cognitive Injury Induced by Heavy Ion Radiation in Male Mice and Alters Behavior and Brain Connectivity.
复制标题
DOI：
10.3389/fphys.2021.770502
复制
发表时间：
2021
影响因子：
4
通讯作者：
Raber J
中科院分区：
文献类型：
--
作者：
Boutros SW;Zimmerman B;Nagy SC;Lee JS;Perez R;Raber J
深空环境对宇航员在太空任务中存在许多风险，例如由自然产生的重离子组成的银河宇宙射线(GCR)。重离子辐射正越来越多地被用于癌症治疗，包括涉及碳治疗的新疗法。之前涉及模拟太空辐射的研究表明，这会对认知和行为产生一系列有害影响。因此，越来越需要抵消重离子辐射的这些有害影响。在这里，我们评估了氨磷汀减轻模拟GCR对C57BL/6J雄性和雌性小鼠的认知损伤的能力。6个月龄小鼠在接受500mGy射线或假照射的简化五离子辐射(质子、28Si、4He、16O和56Fe)前1h，接受生理盐水、107 mg/kg或214 mg/kg氨磷汀的腹腔注射。2-3个月后对小鼠进行行为学测试。接受生理盐水和辐射暴露的雄性小鼠未能表现出新的物体识别，这一点被两种剂量的氨磷汀逆转。相反，接受生理盐水和辐射暴露的雌性小鼠表现出完整的物体识别，但那些在辐射前接受氨磷汀的小鼠则不是这样。在野外，氨磷汀和辐射对雄性和雌性也有不同的影响，氨磷汀影响两性随着时间推移移动的距离，辐射只影响雌性在中心停留的时间。对雄性小鼠CFOS免疫反应的全脑分析表明，氨磷汀和辐射改变了涉及新物体识别的区域的区域连接。这些数据支持氨磷汀有潜力作为对抗质子和重离子照射后男性认知损伤的对策。
The deep space environment contains many risks to astronauts during space missions, such as galactic cosmic rays (GCRs) comprised of naturally occurring heavy ions. Heavy ion radiation is increasingly being used in cancer therapy, including novel regimens involving carbon therapy. Previous investigations involving simulated space radiation have indicated a host of detrimental cognitive and behavioral effects. Therefore, there is an increasing need to counteract these deleterious effects of heavy ion radiation. Here, we assessed the ability of amifostine to mitigate cognitive injury induced by simulated GCRs in C57Bl/6J male and female mice. Six-month-old mice received an intraperitoneal injection of saline, 107 mg/kg, or 214 mg/kg of amifostine 1 h prior to exposure to a simplified five-ion radiation (protons, 28Si, 4He, 16O, and 56Fe) at 500 mGy or sham radiation. Mice were behaviorally tested 2–3 months later. Male mice that received saline and radiation exposure failed to show novel object recognition, which was reversed by both doses of amifostine. Conversely, female mice that received saline and radiation exposure displayed intact object recognition, but those that received amifostine prior to radiation did not. Amifostine and radiation also had distinct effects on males and females in the open field, with amifostine affecting distance moved over time in both sexes, and radiation affecting time spent in the center in females only. Whole-brain analysis of cFos immunoreactivity in male mice indicated that amifostine and radiation altered regional connectivity in areas involved in novel object recognition. These data support that amifostine has potential as a countermeasure against cognitive injury following proton and heavy ion irradiation in males.
登录
查看更多内容
影响因子：
4.4
作者：
Impey S;Pelz C;Tafessu A;Marzulla T;Turker MS;Raber J
通讯作者：
Raber J
DOI：
10.1016/0169-328x(93)90012-e
发表时间：
1993-03-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
DEMMER, J;DRAGUNOW, M;TATE, WP
通讯作者：
TATE, WP
DOI：
10.1016/j.ijrobp.2016.10.001
发表时间：
2017-01-01
影响因子：
7
作者：
Higgins, Kristin A.;O'Connell, Kelli;Behera, Madhusmita
通讯作者：
Behera, Madhusmita
影响因子：
3.4
作者：
Allen, Antino R.;Raber, Jacob;Fike, John R.
通讯作者：
Fike, John R.
乳腺癌幸存者静息态海马功能网络的改变与化疗引起的前瞻性记忆损伤相关
影响因子：
4.6
作者：
Cheng H;Li W;Gong L;Xuan H;Huang Z;Zhao H;Wang LS;Wang K
通讯作者：
Wang K