CNRS, INCC, UMR 8002, Université Paris Cité, F-75006 Paris, France.
INSERM, SAINBIOSE U1059, Mines Saint-Etienne, Université Jean Monnet Saint-Étienne, F-42023 Saint-Étienne, France.
Cells. 2023 Feb 24;12(5):734. doi: 10.3390/cells12050734.
The earliest effect of spaceflight is an alteration in vestibular function due to microgravity. Hypergravity exposure induced by centrifugation is also able to provoke motion sickness. The blood-brain barrier (BBB) is the crucial interface between the vascular system and the brain to ensure efficient neuronal activity. We developed experimental protocols of hypergravity on C57Bl/6JRJ mice to induce motion sickness and reveal its effects on the BBB. Mice were centrifuged at 2× for 24 h. Fluorescent dextrans with different sizes (40, 70 and 150 kDa) and fluorescent antisense oligonucleotides (AS) were injected into mice retro-orbitally. The presence of fluorescent molecules was revealed by epifluorescence and confocal microscopies in brain slices. Gene expression was evaluated by RT-qPCR from brain extracts. Only the 70 kDa dextran and AS were detected in the parenchyma of several brain regions, suggesting an alteration in the BBB. Moreover, Ctnnd1, Gja4 and Actn1 were upregulated, whereas Jup, Tjp2, Gja1, Actn2, Actn4, Cdh2 and Ocln genes were downregulated, specifically suggesting a dysregulation in the tight junctions of endothelial cells forming the BBB. Our results confirm the alteration in the BBB after a short period of hypergravity exposure.
航天飞行的最早影响是由于微重力导致前庭功能改变。离心力引起的超重也能够引发晕动病。血脑屏障 (BBB) 是血管系统和大脑之间的关键界面，可确保有效的神经元活动。我们开发了 C57Bl/6JRJ 小鼠超重的实验方案，以诱导晕动病并揭示其对 BBB 的影响。将小鼠在 2× 下离心 24 小时。将不同大小的荧光葡聚糖（40、70 和 150 kDa）和荧光反义寡核苷酸 (AS) 经眼眶后注射到小鼠体内。通过脑切片的荧光显微镜和共聚焦显微镜揭示荧光分子的存在。通过 RT-qPCR 从脑提取物评估基因表达。只有 70 kDa 葡聚糖和 AS 被检测到在几个脑区的实质中，表明 BBB 发生改变。此外，Ctnnd1、Gja4 和 Actn1 上调，而 Jup、Tjp2、Gja1、Actn2、Actn4、Cdh2 和 Ocln 基因下调，具体表明内皮细胞形成 BBB 的紧密连接失调。我们的结果证实了短暂超重暴露后 BBB 的改变。
