Tsybko A S, Ilchibaeva T V, Kulikov A V, Kulikova E A, Krasnov I B, Sychev V N, Shenkman B S, Popova N K, Naumenko V S
Department of Behavioral Neurogenomics, The Federal Research Center Institute of Cytology and Genetics, Novosibirsk, Russia.
Department of Physiology, Novosibirsk State University, Novosibirsk, Russia.
J Neurosci Res. 2015 Sep;93(9):1399-404. doi: 10.1002/jnr.23600. Epub 2015 May 6.
Mice were exposed to 1 month of space flight on the Russian biosatellite BION-M1 to determine its effect on the expression of genes involved in the maintenance of the mouse brain dopamine system. The current article focuses on the genes encoding glial cell line-derived neurotrophic factor (GDNF) and cerebral dopamine neurotrophic factor (CDNF). Space flight reduced expression of the GDNF gene in the striatum and hypothalamus but increased it in the frontal cortex and raphe nuclei area. At the same time, actual space flight reduced expression of the gene encoding CDNF in the substantia nigra but increased it in the raphe nuclei area. To separate the effects of space flight from environmental stress contribution, we analyzed expression of the investigated genes in mice housed for 1 month on Earth in the same shuttle cabins that were used for space flight and in mice of the vivarium control group. Shuttle cabin housing failed to alter the expression of the GDNF and CDNF genes in the brain structures investigated. Thus, actual long-term space flight produced dysregulation in genetic control of GDNF and CDNF genes. These changes may be related to downregulation of the dopamine system after space flight, which we have shown earlier. © 2015 Wiley Periodicals, Inc.
Our results provide the first evidence of microgravity effects on expression of the GDNF and CDNF neurotrophic factor genes. A considerable decrease in mRNA level of GDNF and CDNF in the nigrostriatal dopamine system was found. Because both GDNF and CDNF play a significant role in maintenance and survival of brain dopaminergic neurons, we can assume that this dysregulation in genetic control of GDNF and CDNF genes in substantia nigra could be among the reasons for the deleterious effects of space flight on the dopamine system.
将小鼠置于俄罗斯生物卫星BION-M1上进行1个月的太空飞行，以确定其对参与维持小鼠脑多巴胺系统的基因表达的影响。本文重点关注编码胶质细胞源性神经营养因子（GDNF）和脑源性多巴胺神经营养因子（CDNF）的基因。太空飞行使纹状体和下丘脑的GDNF基因表达降低，但使额叶皮质和中缝核区域的表达增加。同时，实际太空飞行使黑质中编码CDNF的基因表达降低，但使中缝核区域的表达增加。为了区分太空飞行的影响与环境应激的作用，我们分析了在地球上与太空飞行所用相同的航天舱中饲养1个月的小鼠以及饲养室对照组小鼠中所研究基因的表达。在航天舱中饲养未能改变所研究脑区中GDNF和CDNF基因的表达。因此，实际的长期太空飞行导致了GDNF和CDNF基因遗传调控的失调。这些变化可能与我们之前所表明的太空飞行后多巴胺系统的下调有关。© 2015威利期刊公司。
我们的结果首次提供了微重力对GDNF和CDNF神经营养因子基因表达影响的证据。发现黑质纹状体多巴胺系统中GDNF和CDNF的mRNA水平显著降低。由于GDNF和CDNF在脑多巴胺能神经元的维持和存活中都起着重要作用，我们可以假设黑质中GDNF和CDNF基因遗传调控的这种失调可能是太空飞行对多巴胺系统产生有害影响的原因之一。
