Exposure to mission relevant doses of 1 GeV/Nucleon (56)Fe particles leads to impairment of attentional set-shifting performance in socially mature rats.
Exposure to mission relevant doses of 1 GeV/Nucleon (56)Fe particles leads to impairment of attentional set-shifting performance in socially mature rats.
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DOI：
10.1667/rr3766.1
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发表时间：
2014-09
影响因子：
3.4
通讯作者：
Lonart G
中科院分区：
文献类型：
--
作者：
Britten RA;Davis LK;Jewell JS;Miller VD;Hadley MM;Sanford LD;Machida M;Lonart G
以前的地面实验表明，头部照射与使命相关（20 cGy）剂量的1 GeV/核子56 Fe粒子导致显着损害注意力转移（ATSET）的性能，执行功能的措施，在幼年Wistar大鼠。然而，仅使用头部辐射暴露和该研究中使用的大鼠的生物学年龄可能与确定深空飞行宇航员ATSET受损的可能性无关。在这项研究中，我们已经确定的影响，全身暴露于10，15和20 cGy的1 GeV/核子56 Fe粒子的能力（在暴露后三个月）的社会成熟（退休的饲养员）Wistar大鼠进行注意定势转移范式。目前的研究已经确定，全身暴露于15和20（但不是10）cGy的1 GeV/核子56 Fe粒子的结果在幼年和社会成熟的大鼠ATSET的损害。然而，受损的ATSET性能的确切性质不同，这取决于大鼠的年龄，是否使用全身与头部照射和1 GeV/u 56 Fe的剂量。暴露于20 cGy的1 GeV/核子56 Fe粒子的幼年大鼠导致的能力下降，执行内维移位（IDS）的大鼠是否只接受头部或全身曝光。接受全身暴露的幼龄大鼠适应试验和完成维度内移位逆转（IDR）的能力也降低，而仅接受头部暴露的幼龄大鼠完成化合物辨别逆转（CDR）的能力降低。接受10 cGy的1 GeV/核子56 Fe粒子全身照射的社会成熟大鼠在设置转换性能方面没有明显下降;然而，接受15和20 cGy照射的大鼠进行简单辨别（SD）和复合辨别（CD）的能力降低。暴露于20 cGy的1 GeV/核子56 Fe粒子也导致IDR的性能下降，约25%的大鼠无法适应该任务。这些大鼠中的大多数开始挖掘食物奖励，但很快（15秒内）放弃了挖掘，这表明它们已经发展了关于食物获取的适当程序记忆，但无法保持对任务的注意力。我们的初步数据表明，全身暴露于20 cGy的1 GeV/核子56 Fe粒子减少了胆碱能（但不是GABA能）容易释放池（RRP）的神经末梢的基底前脑从社会成熟的大鼠。胆碱能RRP的这种扰动可能直接导致CDR和IDR性能的丧失，并间接[通过内侧前额叶皮层（mPFC）的代谢变化]导致SD和CD性能的丧失。这些研究结果提供了第一个证据表明，注意定势转移性能在社会成熟大鼠受损后，全身暴露于使命相关剂量（15和20 cGy）的1 GeV/核子56 Fe粒子，重要的是，剂量降低到10 cGy防止这种损害。15和20 cGy的1GeV/核子~（56）Fe粒子照射后，大鼠的辨别能力（SD和CD）和逆转学习能力（CDR）均降低，但在20 cGy照射后，大鼠的辨别能力进一步降低，约有25%的大鼠不能保持对任务的注意。这些行为减退与基底前脑内胆碱能RRP的减少有关，这已被证明在调节PFC的活性中起主要作用。
Previous ground-based experiments have shown that cranial irradiation with mission relevant (20 cGy) doses of 1 GeV/nucleon 56Fe particles leads to a significant impairment in Attentional Set Shifting (ATSET) performance, a measure of executive function, in juvenile Wistar rats. However, the use of head only radiation exposure and the biological age of the rats used in that study may not be pertinent to determine the likelihood that ATSET will be impaired in Astronauts on deep space flights. In this study we have determined the impact that whole-body exposure to 10, 15 and 20 cGy of 1 GeV/nucleon 56Fe particles had on the ability (at three months post exposure) of socially mature (retired breeder) Wistar rats to conduct the attentional set-shifting paradigm. The current study has established that whole-body exposures to 15 and 20 (but not 10) cGy of 1 GeV/nucleon 56Fe particles results in the impairment of ATSET in both juvenile and socially mature rats. However, the exact nature of the impaired ATSET performance varied depending upon the age of the rats, whether whole-body versus cranial irradiation was used and the dose of 1 GeV/u 56Fe received. Exposure of juvenile rats to 20 cGy of 1 GeV/nucleon 56Fe particles led to a decreased ability to perform intra-dimensional shifting (IDS) irrespective of whether the rats received head only or whole-body exposures. Juvenile rats that received whole-body exposure also had a reduced ability to habituate to the assay and to complete intra-dimensional shifting reversal (IDR), whereas juvenile rats that received head only exposure had a reduced ability to complete compound discrimination reversal (CDR). Socially mature rats that received whole-body exposures to 10 cGy of 1 GeV/nucleon 56Fe particles exhibited no obvious decline in set-shifting performance; however those exposed to 15 and 20 cGy had a reduced ability to perform simple discrimination (SD) and compound discrimination (CD). Exposure to 20 cGy of 1 GeV/nucleon 56Fe particles also led to a decreased performance in IDR and to ∼25% of rats failing to habituate to the task. Most of these rats started to dig for the food reward but rapidly (within 15 s) gave up digging, suggesting that they had developed appropriate procedural memories about food retrieval, but had an inability to maintain attention on the task. Our preliminary data suggests that whole-body exposure to 20 cGy of 1 GeV/nucleon 56Fe particles reduced the cholinergic (but not the GABAergic) readily releasable pool (RRP) in nerve terminals of the basal forebrain from socially-mature rats. This perturbation of the cholinergic RRP could directly lead to the loss of CDR and IDR performance, and indirectly [through the metabolic changes in the medial prefrontal cortex (mPFC)] to the loss of SD and CD performance. These findings provide the first evidence that attentional set-shifting performance in socially mature rats is impaired after whole-body exposure to mission relevant doses (15 and 20 cGy) of 1 GeV/nucleon 56Fe particles, and importantly that a dose reduction down to 10 cGy prevents that impairment. The ability to conduct Discrimination tasks (SD and CD) and reversal learning (CDR) is reduced after exposure to 15 and 20 cGy of 1 GeV/nucleon 56Fe particles, but at 20 cGy there is an additional decrement, ∼ 25% of rats are unable to maintain attention to task. These behavioral decrements are associated with a reduction in the cholinergic RRP within basal forebrain, which has been shown to play a major role in regulating the activity of the PFC.