Pompeiano M, d'Ascanio P, Centini C, Pompeiano O, Balaban E
Dipartimento di Scienze dell'Uomo e dell'Ambiente, Universitá di Pisa, Scuola Medica, Via Roma 55, I-56126 Pisa, Italy.
Neuroscience. 2002;115(1):111-23. doi: 10.1016/s0306-4522(02)00402-5.
Changes in immediate-early gene (IEG) expression during and after space flight were studied in the rat locus coeruleus (LC) during the NASA Neurolab mission. The LC sends widespread projections throughout the brain and releases the neuromodulator norepinephrine. LC neurons respond to natural vestibular stimulation; their firing rate also increases during waking and decreases or ceases during sleep. LC neurons express IEGs such as c-fos after activation. Adult male albino Fisher 344 rats were killed at four mission time points, and the number of Fos- and Fos-related antigen (FRA)-positive LC cells were counted in flight and ground-based control rats. Half of the subjects at each time point were exposed to light for 60 min prior to killing to standardize their sleep-waking state. FRA-expressing cells were more numerous than Fos-expressing cells in both flight- and ground-based subjects. The difference between FRA- and Fos-expressing cells within individuals was significantly larger 24 h after landing in subjects exposed to both space flight and light pulse than in all other subjects at any mission time point. Fos and FRA responses scaled in proportion to the maximum response observed in any single individual showed similar patterns of variation. Analysis of the scaled and combined responses showed that LC IEG levels responded to both gravity changes and light pulses. Subjects exposed to either single stimulus had equivalent responses, significantly greater than those of control subjects maintained in dim light. The combination of gravity change and light pulse gave significantly higher LC responses than either stimulus alone 24 h after takeoff, and to a lesser extent after 12 days in space; the highest responses were obtained 24 h after landing. By 14 days after landing, animals exposed to space flight and light pulse responded no differently than ground-based subjects. No difference in LC IEG expression was clearly attributable to changes in the sleep-waking state of subjects. Activity of noradrenergic LC neurons has been previously shown to modulate IEG expression in target structures. The increased IEG LC activity (seen most especially 24 h after landing) may reflect large-scale activation of noradrenergic neurons that may serve as a trigger for molecular changes in target structures, and be critical for adaptation to gravity changes.
在NASA神经实验室任务期间，对大鼠蓝斑（LC）在太空飞行期间及之后即刻早期基因（IEG）表达的变化进行了研究。蓝斑向整个大脑广泛投射，并释放神经调质去甲肾上腺素。蓝斑神经元对自然前庭刺激有反应；它们的放电频率在清醒时增加，在睡眠时降低或停止。蓝斑神经元在激活后会表达如c-fos等即刻早期基因。成年雄性白化病Fisher 344大鼠在四个任务时间点被处死，对飞行组和地面对照组大鼠中Fos和Fos相关抗原（FRA）阳性的蓝斑细胞数量进行计数。每个时间点的一半受试者在处死前暴露于光照60分钟，以标准化其睡眠-觉醒状态。在飞行组和地面组受试者中，表达FRA的细胞都比表达Fos的细胞多。在暴露于太空飞行和光脉冲的受试者中，着陆后24小时内个体中表达FRA和Fos的细胞之间的差异明显大于任何任务时间点的所有其他受试者。Fos和FRA反应与在任何单个个体中观察到的最大反应成比例缩放，显示出相似的变化模式。对缩放后的综合反应进行分析表明，蓝斑即刻早期基因水平对重力变化和光脉冲均有反应。暴露于单一刺激的受试者有同等的反应，明显大于在昏暗光线下的对照组受试者。重力变化和光脉冲的组合在起飞后24小时产生的蓝斑反应明显高于单独的任何一种刺激，在太空飞行12天后程度较小；着陆后24小时获得最高反应。到着陆后14天，暴露于太空飞行和光脉冲的动物与地面组受试者的反应没有差异。蓝斑即刻早期基因表达的差异没有明显归因于受试者睡眠-觉醒状态的变化。先前已表明去甲肾上腺素能蓝斑神经元的活动可调节靶结构中的即刻早期基因表达。即刻早期基因蓝斑活动增加（在着陆后24小时最为明显）可能反映出去甲肾上腺素能神经元的大规模激活，这可能是靶结构分子变化的触发因素，对适应重力变化至关重要。
