Pulga Alice, Porte Yves, Morel Jean-Luc
Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293Bordeaux, France; Centre National de la Recherche Scientifique, Institut des Maladies Neurodégénératives, UMR 5293Bordeaux, France.
Front Mol Neurosci. 2016 Dec 26;9:153. doi: 10.3389/fnmol.2016.00153. eCollection 2016.
Centrifugation is a widely used procedure to study the impact of altered gravity on Earth, as observed during spaceflights, allowing us to understand how a long-term physical constraint can condition the mammalian physiology. It is known that mice, placed in classical cages and maintained during 21 days in a centrifuge at 3G gravity level, undergo physiological adaptations due to hypergravity, and/or stress. Indeed, an increase of corticosterone levels has been previously measured in the plasma of 3G-exposed mice. Corticosterone is known to modify neuronal activity during memory processes. Although learning and memory performances cannot be assessed during the centrifugation, literature largely described a large panel of proteins (channels, second messengers, transcription factors, structural proteins) which expressions are modified during memory processing. Thus, we used the Illumina technology to compare the whole hippocampal transcriptome of three groups of C57Bl6/J mice, in order to gain insights into the effects of hypergravity on cerebral functions. Namely, a group of 21 days 3G-centrifuged mice was compared to (1) a group subjected to an acute corticosterone injection, (2) a group receiving a transdermal chronic administration of corticosterone during 21 days, and (3) aged mice because aging could be characterized by a decrease of hippocampus functions and memory impairment. Our results suggest that hypergravity stress induced by corticosterone administration and aging modulate the expression of genes in the hippocampus. However, the modulations of the transcriptome observed in these conditions are not identical. Hypergravity affects the hippocampus transcriptome and probably modifies its activity. Hypergravity induced changes in hippocampal transcriptome were more similar to acute injection than chronic diffusion of corticosterone or aging.
离心是一种广泛应用的程序,用于研究地球重力变化的影响,就像在太空飞行中观察到的那样,使我们能够了解长期的物理限制如何影响哺乳动物的生理机能。众所周知,将小鼠置于传统笼子中,在3G重力水平的离心机中饲养21天,由于超重和/或应激,它们会发生生理适应。事实上,先前已测量到暴露于3G环境的小鼠血浆中皮质酮水平升高。已知皮质酮会在记忆过程中改变神经元活动。虽然在离心过程中无法评估学习和记忆表现,但文献中大量描述了一大类蛋白质(通道、第二信使、转录因子、结构蛋白),其表达在记忆处理过程中会发生改变。因此,我们使用Illumina技术比较了三组C57Bl6/J小鼠的全海马转录组,以深入了解超重对脑功能的影响。具体来说,将一组经过21天3G离心的小鼠与(1)一组接受急性皮质酮注射的小鼠、(2)一组在21天内接受皮质酮经皮慢性给药的小鼠以及(3)老年小鼠进行比较,因为衰老可能表现为海马功能下降和记忆障碍。我们的结果表明,皮质酮给药和衰老诱导的超重应激会调节海马体中基因的表达。然而,在这些条件下观察到的转录组调节并不相同。超重会影响海马转录组,并可能改变其活性。超重诱导的海马转录组变化与急性注射比与皮质酮慢性扩散或衰老更相似。