Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

Abstract

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 per-se 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.

Effects of centrifugation and whole-body vibrations on blood–brain barrier permeability in mice

“…As previously shown, the increase of body weight was reduced after a long-lasting exposure to HG, which has been proposed as an index of the centrifugation. [20][21][22] We have pinpointed that this reduction started as soon as the first day of centrifugation. One factor involved in this weight reduction could be the decrease of food intake provoked by vestibular over stimulation, as we recently demonstrated during short-term motion sickness protocols.…”

“…Finally, although the impairment in memory processes in people exposed to WBV are not clearly demonstrated, 32,33 several studies in mice have suggested that alterations of spatial navigation and memory could be induced by gravity changes. 34 This is supported by transcriptomic and proteomic analysis of brain in mice models, 22,35,36 and more recently in humans by magnetic resonance imaging. 4,[37][38][39][40] As also proposed in the field of neurodegenerative disorders, an impairment of the BBB is suggested to induce or accelerate the processes of the memory impairments.…”

Artificial hibernation/life-protective state induced by thiazoline-related innate fear odors

“…To analyze the effects of corticosterone, C57BL/6 mice were IP injected with saline or corticosterone 16 , 64 , 65 (2 mg/kg; Sigma-Aldrich). At 30 min after drug administration, survival times under 4% oxygen were analyzed as described above.…”

On the Mechanism of Action of Anti-Inflammatory Activity of Hypericin: An In Silico Study Pointing to the Relevance of Janus Kinases Inhibition

“…GOLD implements a genetic algorithm that may introduce variability in the results in a system-dependent manner possibly causing outliers. Therefore, outlier points were removed to a maximum of one for each run after being identified with the modified Thompson Tau Test, as already reported [55]. Data were statistically compared by one-way ANOVA (α = 0.05), using IBM SPSS Statistics for Linux, version 25 (IBM Corp., Armonk, NY, USA).…”