Department of Behavioral Neuroscience, Oregon Health Science University, Portland, OR 97239, USA.
Knight Flow Cytometry Core OHSU, Portland, OR 97239, USA.
Int J Mol Sci. 2023 Aug 6;24(15):12497. doi: 10.3390/ijms241512497.
We assessed the effects of conventional and ultra-high dose rate (UHDR) electron irradiation on behavioral and cognitive performance one month following exposure and assessed whether these effects were associated with alterations in the number of immune cells in the hippocampus using flow cytometry. Two-month-old female and male C57BL/6J mice received whole-brain conventional or UHDR irradiation. UHDR mice were irradiated with 9 MeV electrons, delivered by the Linac-based/modified beam control. The mice were irradiated or sham-irradiated at Dartmouth, the following week shipped to OHSU, and behaviorally and cognitively tested between 27 and 41 days after exposure. Conventional- and UHDR-irradiated mice showed impaired novel object recognition. During fear learning, conventional- and UHDR-irradiated mice moved less during the inter-stimulus interval (ISI) and UHDR-irradiated mice also moved less during the baseline period (prior to the first tone). In irradiated mice, reduced activity levels were also seen in the home cage: conventional- and UHDR-irradiated mice moved less during the light period and UHDR-irradiated mice moved less during the dark period. Following behavioral and cognitive testing, infiltrating immune cells in the hippocampus were analyzed by flow cytometry. The percentage of Ly6G+ CD45+ cells in the hippocampus was lower in conventional- and UHDR-irradiated than sham-irradiated mice, suggesting that neutrophils might be particularly sensitive to radiation. The percentage of Ly6G+ CD45+ cells in the hippocampus was positively correlated with the time spent exploring the novel object in the object recognition test. Under the experimental conditions used, cognitive injury was comparable in conventional and UHDR mice. However, the percentage of CD45+ CD11b+ Ly6+ and CD45+ CD11b+ Ly6G- cells in the hippocampus cells in the hippocampus was altered in conventional- but not UHDR-irradiated mice and the reduced percentage of Ly6G+ CD45+ cells in the hippocampus might mediate some of the detrimental radiation-induced cognitive effects.
我们评估了常规和超高剂量率（UHDR）电子照射对暴露后一个月行为和认知表现的影响，并使用流式细胞术评估这些影响是否与海马体中免疫细胞数量的变化有关。两个月大的雌性和雄性 C57BL/6J 小鼠接受全脑常规或 UHDR 照射。UHDR 小鼠接受 9 MeV 电子照射，由基于直线加速器/改良束流控制的直线加速器提供。小鼠在 Dartmouth 接受照射或假照射，接下来一周运到 OHSU，并在暴露后 27 至 41 天进行行为和认知测试。常规和 UHDR 照射的小鼠在新物体识别中表现出受损。在恐惧学习过程中，常规和 UHDR 照射的小鼠在刺激间隔（ISI）期间移动较少，而 UHDR 照射的小鼠在基线期（第一声之前）期间也移动较少。在照射的小鼠中，在家庭笼中也观察到活动水平降低：常规和 UHDR 照射的小鼠在光照期移动较少，而 UHDR 照射的小鼠在暗期移动较少。在行为和认知测试后，通过流式细胞术分析海马体中的浸润免疫细胞。与假照射的小鼠相比，常规和 UHDR 照射的小鼠海马体中的 Ly6G+CD45+细胞百分比较低，提示中性粒细胞可能对辐射特别敏感。海马体中 Ly6G+CD45+细胞的百分比与物体识别测试中探索新物体的时间呈正相关。在使用的实验条件下，常规和 UHDR 小鼠的认知损伤相当。然而，海马体中 CD45+CD11b+Ly6+和 CD45+CD11b+Ly6G-细胞的百分比在常规照射而不是 UHDR 照射的小鼠中发生改变，而海马体中 Ly6G+CD45+细胞的百分比降低可能介导一些有害的辐射诱导的认知效应。
