Evaluation of Gene, Protein and Neurotrophin Expression in the Brain of Mice Exposed to Space Environment for 91 Days

Effects of 3-month exposure to microgravity environment on the expression of genes and proteins in mouse brain were studied. Moreover, responses of neurobiological parameters, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF), were also evaluated in the cerebellum, hippocampus, cortex, and adrenal glands. Spaceflight-related changes in gene and protein expression were observed. Biological processes of the up-regulated genes were related to the immune response, metabolic process, and/or inflammatory response. Changes of cellular components involving in microsome and vesicular fraction were also noted. Molecular function categories were related to various enzyme activities. The biological processes in the down-regulated genes were related to various metabolic and catabolic processes. Cellular components were related to cytoplasm and mitochondrion. The down-regulated molecular functions were related to catalytic and oxidoreductase activities. Up-regulation of 28 proteins was seen following spaceflight vs. those in ground control. These proteins were related to mitochondrial metabolism, synthesis and hydrolysis of ATP, calcium/calmodulin metabolism, nervous system, and transport of proteins and/or amino acids. Down-regulated proteins were related to mitochondrial metabolism. Expression of NGF in hippocampus, cortex, and adrenal gland of wild type animal tended to decrease following spaceflight. As for pleiotrophin transgenic mice, spaceflight-related reduction of NGF occured only in adrenal gland. Consistent trends between various portions of brain and adrenal gland were not observed in the responses of BDNF to spaceflight. Although exposure to real microgravity influenced the expression of a number of genes and proteins in the brain that have been shown to be involved in a wide spectrum of biological function, it is still unclear how the functional properties of brain were influenced by 3-month exposure to microgravity.

本研究探讨了为期3个月的微重力环境暴露对小鼠脑内基因与蛋白质表达的影响。此外，本研究还检测了小脑、海马体、大脑皮层及肾上腺中神经生物学参数、神经生长因子（nerve growth factor, NGF）与脑源性神经营养因子（brain derived neurotrophic factor, BDNF）的响应变化。研究观测到航天相关的基因与蛋白质表达改变：上调基因的生物学过程主要涉及免疫应答、代谢过程及炎症应答；同时还发现涉及微粒体与囊泡组分的细胞组分变化。分子功能类别则与多种酶活性相关。下调基因的生物学过程涵盖各类代谢与分解代谢过程，相关细胞组分包括细胞质与线粒体；下调的分子功能则与催化活性及氧化还原酶活性相关。相较于地面对照组，航天暴露后共有28种蛋白质表达上调，这些蛋白质主要与线粒体代谢、ATP合成与水解、钙/钙调蛋白代谢、神经系统功能以及蛋白质/氨基酸转运相关。下调蛋白质则与线粒体代谢相关。航天暴露后，野生型小鼠海马体、大脑皮层及肾上腺内的NGF表达呈下降趋势；而在多效生长因子（pleiotrophin）转基因小鼠中，航天相关的NGF表达降低仅出现于肾上腺组织中。在BDNF对航天暴露的响应中，未观测到脑内各区域与肾上腺间的一致变化趋势。尽管真实微重力暴露影响了小鼠脑内众多参与广泛生物学功能的基因与蛋白质的表达，但目前仍不清楚为期3个月的微重力暴露如何影响大脑的功能特性。