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太空飞行期间及之后大鼠前庭和网状结构中的基因表达

Gene expression in rat vestibular and reticular structures during and after space flight.

作者信息

Pompeiano O, d'Ascanio P, Centini C, Pompeiano M, Balaban E

机构信息

Dipartimento di Fisiologia e Biochimica, Università di Pisa, Via S. Zeno 31, I-56127 Pisa, Italy.

出版信息

Neuroscience. 2002;114(1):135-55. doi: 10.1016/s0306-4522(02)00202-6.

Abstract

Space flight produces profound changes of neuronal activity in the mammalian vestibular and reticular systems, affecting postural and motor functions. These changes are compensated over time by plastic alterations in the brain. Immediate early genes (IEGs) are useful indicators of both activity changes and neuronal plasticity. We studied the expression of two IEG protein products [Fos and Fos-related antigens (FRAs)] with different cell persistence times (hours and days, respectively) to identify brainstem vestibular and reticular structures involved in adaptation to microgravity and readaptation to 1 G (gravity) during the NASA Neurolab Mission (STS-90). IEG protein expression in flight animals was compared to that of ground controls using Fisher 344 rats killed 1 and 12 days after launch and 1 and 14 days after landing. An increase in the number of Fos-protein-positive cells in vestibular (especially medial and spinal) regions was observed 1 day after launch and 1 day after landing. Fos-positive cell numbers were no different from controls 12 days after launch or 14 days after landing. No G-related changes in IEG expression were observed in the lateral vestibular nucleus. The pattern of FRA protein expression was generally similar to that of Fos, except at 1 day after landing, when FRA-expressing cells were observed throughout the whole spinal vestibular nucleus, but only in the caudal part of the medial vestibular nucleus. Fos expression was found throughout the entire medial vestibular nucleus at this time. While both Fos and FRA expression patterns may reflect the increased G force experienced during take-off and landing, the Fos pattern may additionally reflect recent rebound episodes of rapid eye movement (REM) sleep following forced wakefulness, especially after landing. Pontine activity sources producing rhythmic discharges of vestibulo-oculomotor neurons during REM sleep could substitute for labyrinthine signals after exposure to microgravity, contributing to activity-related plastic changes leading to G readaptation. Reticular structures exhibited a contrasting pattern of changes in the numbers of Fos- and FRA-positive cells suggestive of a major influence from proprioceptive inputs, and plastic re-weighting of inputs after landing. Asymmetric induction of Fos and FRAs observed in some vestibular nuclei 1 day after landing suggests that activity asymmetries between bilateral otolith organs, their primary labyrinthine afferents, and vestibular nuclei may become unmasked during flight.

摘要

太空飞行会使哺乳动物的前庭和网状系统中的神经元活动产生深刻变化,从而影响姿势和运动功能。随着时间的推移,这些变化会通过大脑中的可塑性改变得到补偿。即刻早期基因(IEGs)是活动变化和神经元可塑性的有用指标。我们研究了两种具有不同细胞持续时间(分别为小时和天)的即刻早期基因蛋白产物[Fos和Fos相关抗原(FRAs)]的表达,以确定在美国国家航空航天局神经实验室任务(STS - 90)期间参与适应微重力和重新适应1G(重力)的脑干前庭和网状结构。将飞行动物的即刻早期基因蛋白表达与发射后1天和12天以及着陆后1天和14天处死的地面对照Fisher 344大鼠的表达进行比较。发射后1天和着陆后1天观察到前庭(尤其是内侧和脊髓)区域中Fos蛋白阳性细胞数量增加。发射后12天或着陆后14天,Fos阳性细胞数量与对照无差异。在外侧前庭核中未观察到与重力相关的即刻早期基因表达变化。FRA蛋白表达模式总体上与Fos相似,除了着陆后1天,此时在整个脊髓前庭核中观察到FRA表达细胞,但仅在内侧前庭核的尾部观察到。此时在整个内侧前庭核中均发现了Fos表达。虽然Fos和FRA的表达模式都可能反映起飞和着陆期间所经历的重力增加,但Fos模式可能还额外反映了强制清醒后快速眼动(REM)睡眠最近的反弹发作,尤其是着陆后。在REM睡眠期间产生前庭动眼神经元节律性放电的脑桥活动源,在暴露于微重力后可以替代迷路信号,促成与活动相关的可塑性变化,从而导致重力重新适应。网状结构在Fos和FRA阳性细胞数量上呈现出相反的变化模式,这表明本体感受输入有重大影响,并且着陆后输入进行了可塑性重新加权。着陆后1天在一些前庭核中观察到的Fos和FRAs的不对称诱导表明,双侧耳石器官、其主要迷路传入神经和前庭核之间的活动不对称可能在飞行期间被揭示出来。

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