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暴露于 5 cGy 28Si 粒子会导致纹状体和侧脑室下区的小胶质细胞长期激活,并伴有神经发生抑制。

Exposure to 5 cGy 28Si Particles Induces Long-Term Microglial Activation in the Striatum and Subventricular Zone and Concomitant Neurogenic Suppression.

机构信息

Research Service, Edward Hines Jr. VA Hospital, Hines, Illinois.

Department of Psychology, Northern Illinois University, DeKalb, Illinois.

出版信息

Radiat Res. 2022 Jul 1;198(1):28-39. doi: 10.1667/RADE-21-00021.1.

DOI:10.1667/RADE-21-00021.1
PMID:35377458
Abstract

The proposed mission to Mars will expose astronauts to space radiation that is known to adversely affect cognition and tasks that rely on fine sensorimotor function. Space radiation has also been shown to affect the microglial and neurogenic responses in the central nervous system (CNS). We recently reported that a low dose of 5 cGy 600 MeV/n 28Si results in impaired cognition and skilled motor behavior in adult rats. Since these tasks rely at least in part on the proper functioning of the striatum, we examined striatal microglial cells in these same subjects. Using morphometric analysis, we found that 28Si exposure increased activated microglial cells in the striatum. The majority of these striatal Iba1+ microglia were ED1-, indicating that they were in an alternatively activated state, where microglia do not have phagocytic activity but may be releasing cytokines that could negatively impact neuronal function. In the other areas studied, Iba1+ microglial cells were increased in the subventricular zone (SVZ), but not in the dentate gyrus (DG). Additionally, we examined the relationship between the microglial response and neurogenesis. An analysis of new neurons in the DG revealed an increase in doublecortin-positive (DCX+) hilar ectopic granule cells (hEGC) which correlated with Iba1+ cells, suggesting that microglial cells contributed to this aberrant distribution which may adversely affect hippocampal function. Taken together, these results indicate that a single dose of 28Si radiation results in persistent cellular effects in the CNS that may impact astronauts both in the short and long-term following deep space missions.

摘要

拟议的火星任务将使宇航员暴露在已知会对认知和依赖精细感觉运动功能的任务产生不利影响的空间辐射中。空间辐射也已被证明会影响中枢神经系统(CNS)中的小胶质细胞和神经发生反应。我们最近报告称,低剂量的 5 cGy 600 MeV/n 28Si 会导致成年大鼠认知和熟练运动行为受损。由于这些任务至少部分依赖于纹状体的正常功能,我们在这些相同的实验对象中检查了纹状体中小胶质细胞。使用形态计量学分析,我们发现 28Si 暴露会增加纹状体中的活化小胶质细胞。这些纹状体 Iba1+小胶质细胞中的大多数是 ED1-,表明它们处于一种替代性激活状态,在这种状态下,小胶质细胞没有吞噬活性,但可能释放细胞因子,从而对神经元功能产生负面影响。在研究的其他区域中,SVZ 中的 Iba1+小胶质细胞增加,但 DG 中没有增加。此外,我们还研究了小胶质细胞反应与神经发生之间的关系。DG 中新生神经元的分析显示,双皮质素阳性(DCX+)的齿状回异位颗粒细胞(hEGC)增加,与 Iba1+细胞相关,表明小胶质细胞有助于这种异常分布,可能会对海马功能产生不利影响。总之,这些结果表明,单次 28Si 辐射会导致 CNS 中持续的细胞效应,这可能会对深太空任务后的短期和长期宇航员产生影响。

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