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超重对大鼠发育过程中前庭上皮神经支配成熟的差异影响。

Differential impact of hypergravity on maturating innervation in vestibular epithelia during rat development.

作者信息

Gaboyard Sophie, Sans Alain, Lehouelleur Jacques

机构信息

INSERM U432, Université Montpellier II, place E. Bataillon, 34095 Montpellier, Cedex 05, France.

出版信息

Brain Res Dev Brain Res. 2003 Jun 12;143(1):15-23. doi: 10.1016/s0165-3806(03)00069-5.

Abstract

Over the past decades, the new opportunity of space flights has revealed the importance of gravity as a mechanical constraint for terrestrial organisms as well as its influence on the somatosensory system. The lack of gravitational reference in orbital flight induces changes in equilibrium, with major modifications involving neuromorphological and physiological adaptations. However, few data have illustrated the putative effect of gravity on sensory vestibular epithelial development. We asked if gravity, the primary stimulus of utricles could act as an epigenetic factor. As sensorial deprivation linked to weightlessness is technically difficult, we used a ground-based centrifuge to increase the gravitational vector, in order to hyperstimulate the vestibule. In this study, 3 days after mating, pregnant females were submitted to hypergravity, 2 g (HG). Their embryos were raised, born and postnatally developed under HG. The establishment of connections between primary vestibular afferent neurons and hair cells in the utricle of these young rats was followed from birth to postnatal day 6 (PN6) and compared to embryos developed in normogravity (NG): Immunocytochemistry for neurofilaments and microvesicles revealed the differential effects of gravity on the late neuritogenic and synaptogenic processes in utricles. Taking type I hair cell innervation as a criterion of maturation, we found that primary afferent fibres reached the vestibular epithelium and enveloped hair cells in the same way, both under NG and HG. Thus, this phenomenon of leading growth cones to their epithelial target appears to be dependent on intrinsic genetic properties and not on an external stimulus. In contrast, the maturation of connection processes between type 1 hair cells and the afferent calyx, concerning specifically the microvesicles at their apex, was delayed under HG. Therefore, gravity appears to be an epigenetic factor influencing the late maturation of utricles. These differential effects of altered gravity on the development of the vestibular epithelium are discussed.

摘要

在过去几十年中,太空飞行带来的新机遇揭示了重力作为陆地生物的一种机械性限制因素的重要性及其对体感系统的影响。轨道飞行中缺乏重力参考会引发平衡变化,主要的改变涉及神经形态学和生理学适应。然而,很少有数据阐明重力对感觉性前庭上皮发育的假定作用。我们探究了重力这种椭圆囊的主要刺激因素是否能作为一种表观遗传因子。由于与失重相关的感觉剥夺在技术上具有难度,我们使用地面离心机来增加重力矢量,以便过度刺激前庭。在本研究中,交配后3天,怀孕的雌性大鼠被置于2g的超重环境(HG)中。它们的胚胎在超重环境下生长、出生并在出生后发育。从出生到出生后第6天(PN6),追踪这些幼鼠椭圆囊中初级前庭传入神经元与毛细胞之间连接的建立情况,并与在正常重力(NG)环境下发育的胚胎进行比较:神经丝和微泡的免疫细胞化学揭示了重力对椭圆囊中晚期神经突生成和突触形成过程的不同影响。以I型毛细胞的神经支配作为成熟的标准,我们发现无论是在正常重力还是超重环境下,初级传入纤维都以相同的方式到达前庭上皮并包裹毛细胞。因此,这种引导生长锥到达其上皮靶标的现象似乎取决于内在遗传特性,而非外部刺激。相比之下,在超重环境下,I型毛细胞与传入花萼之间连接过程的成熟,特别是其顶端微泡的成熟,出现了延迟。因此,重力似乎是影响椭圆囊晚期成熟的一种表观遗传因子。本文讨论了重力改变对前庭上皮发育的这些不同影响。

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