Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain.
Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain.
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DOI：
10.1371/journal.pone.0177833
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Shiga T
中科院分区：
文献类型：
--
作者：
Ishikawa C;Li H;Ogura R;Yoshimura Y;Kudo T;Shirakawa M;Shiba D;Takahashi S;Morita H;Shiga T
太空飞行涉及各种压力环境因素，包括微重力。重力变化对骨骼、肌肉、心血管、免疫和前庭系统的影响已被广泛研究，但对神经系统的影响尚未得到充分研究。在地面动物实验中改变重力是解决这一问题的方法之一。本实验研究离心诱导的重力变化对小鼠脑源性神经营养因子（BDNF）和5-羟色胺受体（5-HTRs）基因表达的影响。暴露于2g超重力下14天显示出不同大脑区域基因表达的差异调节。BDNF在海马腹侧和下丘脑的表达减少，而在小脑的表达增加。5-HT1BR在小脑中表达减少，而在海马腹侧和尾状壳核中表达增加。相比之下，超重对5-HT1AR、5-HT2AR、5-HT2CR、5-HT4R和5-HT7R的基因表达没有影响。除超重力外，从2g超重力到1g正常重力的减速重力变化影响了脑各区域BDNF、5-HT1AR、5-HT1BR和5-HT2AR的基因表达。我们还研究了前庭器官在超重力影响中的作用。内耳前庭器官的手术损伤消除了超重对基因表达的影响，这表明超重的影响是通过前庭器官介导的。总之，我们发现重力变化诱导BDNF和5-HT1AR （5-HT1AR、5-HT1BR和5-HT2AR）基因表达的差异调节。基因表达的调节可能构成由重力变化引起的行为改变的分子基础。
Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear’s vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes.