Effect of microgravity on gene expression in mouse brain.
Effect of microgravity on gene expression in mouse brain.
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DOI：
10.1007/s00221-008-1523-5
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发表时间：
2008-11
影响因子：
2
通讯作者：
Spray, David C.
中科院分区：
文献类型：
--
作者：
Frigeri, Antonio;Iacobas, Dumitru A.;Iacobas, Sanda;Nicchia, Grazia Paola;Desaphy, Jean Francois;Camerino, Diana Conte;Svelto, Maria;Spray, David C.
关键词：
重力的变化，例如宇航员在空间飞行中所经历的重力变化，会引起液体从身体的尾部向头部的重新分配，同时消除正常的头到脚的流体静压梯度。为了评估与微重力和液体转移相关的脑基因谱变化，使用cDNA微阵列对2周对照和后肢卸载（HU）小鼠的脑中的mRNA表达水平进行了大规模分析。虽然在不同程度上，所有的功能类别显示显着调节基因，表明相当大的转录组的改变是由HU诱导。有趣的是，TIC类（将小分子和离子转运到细胞中）具有最高百分比的上调基因，而下调最多的基因是JAE类（细胞连接，粘附，细胞外基质）。TIC基因占表达改变的基因的16%，包括钠通道、非电压门控1 β（Scnn 1b）、谷氨酸受体（Grin 1）、电压依赖性阴离子通道1（Vdac 1）、钙通道β 3亚基（Cacnb 3）等。通过Gene-MAPP进行的分析揭示了几种改变的蛋白质类别和功能途径，如血液凝固和免疫反应，学习和记忆，离子通道和细胞连接。特别是，数据表明HU导致止血改变，其以向更高凝血状态的转变而消退，静脉血栓形成风险增加。此外，HU治疗似乎影响突触可塑性和学习过程的关键步骤。
Changes in gravitational force such as that experienced by astronauts during space flight induce a redistribution of fluids from the caudad to the cephalad portion of the body together with an elimination of normal head-to-foot hydrostatic pressure gradients. To assess brain gene profile changes associated with microgravity and fluid shift, a large-scale analysis of mRNA expression levels was performed in the brains of 2-week control and hindlimb-unloaded (HU) mice using cDNA microarrays. Although to different extents, all functional categories displayed significantly regulated genes indicating that considerable transcriptomic alterations are induced by HU. Interestingly, the TIC class (transport of small molecules and ions into the cells) had the highest percentage of up-regulated genes, while the most down-regulated genes were those of the JAE class (cell junction, adhesion, extracellular matrix). TIC genes comprised 16% of those whose expression was altered, including sodium channel, nonvoltage-gated 1 beta (Scnn1b), glutamate receptor (Grin1), voltage-dependent anion channel 1 (Vdac1), calcium channel beta 3 subunit (Cacnb3) and others. The analysis performed by Gene-MAPP revealed several altered protein classes and functional pathways such as blood coagulation and immune response, learning and memory, ion channels and cell junction. In particular, data indicate that HU causes an alteration in hemostasis which resolves in a shift toward a more hyper-coagulative state with an increased risk of venous thrombosis. Furthermore, HU treatment seems to impact on key steps of synaptic plasticity and learning processes.
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