Gene responses in mouse brain to long-term exposure to microgravity

The spaceflight experiment was carried out using male C57BL/10J mice (8 weeks old at launch). Wild type mice (n equals 3) were launched by Space Shuttle Discovery and housed on the International Space Station (ISS) for 91 days. They returned to the Earth by Space Shuttle Atlantis. But only one mouse returned to the Earth alive. Whole brain was sampled from the mouse killed by inhalation of carbon dioxide at the Life Sciences Support Facility of Kennedy Space Center within 3-4 hours after landing. After the spaceflight experiment, the on-ground experiment was also carried out at the Advanced Biotechnology Center in Genova, Italy. A mouse with the same species, sex, and age was housed in mice drawer system (MDS), which was utilized for the spaceflight (SF) mice, for 3 months as the ground control (GC). Another mouse was housed in normal vivarium cage as the laboratory control (LC). Amount of food and water supplementation and environmental conditions were simulated as the flight group. After 3 months, brain was sampled from one mouse in group GC and LC, respectively. Comprehensive analyses of gene expression were performed in the right brain. Total of 4,000 genes were analyzed. The expression levels of 60 genes significantly changed in response to SF compared with LC and/or GC. The 15 and 16 genes were up- (greater than 2 folds) and down-regulated (less than 0.5 folds), respectively, following SF vs. GC. The levels of 58 genes were significantly altered by housing in MDS in space and/or on the ground. Forty seven and 11 genes were significantly up- and down-regulated vs. LC. Twenty seven out of these genes responded to caging in MDS both in space and on the ground. Further, 31 genes were influenced by housing in MDS on the Earth. Responses of the characteristics of brain to long-term gravitational unloading were investigated in mice.

本航天实验以发射时周龄为8周的雄性C57BL/10J小鼠为受试对象。野生型小鼠（样本量n=3）由发现号航天飞机（Space Shuttle Discovery）搭载升空，于国际空间站（International Space Station, ISS）饲养91天，后由亚特兰蒂斯号航天飞机（Space Shuttle Atlantis）返回地球，但仅1只小鼠存活返地。着陆后3-4小时内，科研人员于肯尼迪航天中心（Kennedy Space Center）生命科学支持设施中，通过吸入二氧化碳处死该存活小鼠，并采集其全脑样本。
航天实验结束后，研究团队于意大利热那亚先进生物技术中心开展地面对照实验：选取品系、性别与周龄均一致的小鼠，置于航天飞行（Space Flight, SF）小鼠所用的小鼠笼具系统（Mice Drawer System, MDS）中饲养3个月，作为地面对照（Ground Control, GC）组；另有1只小鼠饲养于普通实验动物饲养笼中，作为实验室对照（Laboratory Control, LC）组。实验过程中，饲料、饮水补给量与环境条件均模拟航天飞行组设置。饲养3个月后，分别从GC组与LC组小鼠体内采集脑组织样本。
研究人员对右侧脑组织开展基因表达综合分析，共检测4000个基因的表达水平。相较于LC组与/或GC组，航天飞行组有60个基因的表达水平发生显著变化：其中15个基因表达上调（倍数≥2）、16个基因表达下调（倍数≤0.5）。相较于LC组，太空及地面环境下使用MDS饲养的小鼠共有58个基因的表达水平发生显著改变，其中47个基因表达上调、11个基因表达下调。此类基因中有27个在太空与地面的MDS饲养环境下均出现表达响应；另有31个基因仅受地球表面MDS饲养环境的影响。本研究还探讨了脑组织特征对长期重力卸载的响应情况。