Several pathophysiological processes involve Hypoxia conditions, where the nervous system is affected as well. We postulate that the GABAergic system is especially sensitive. Furthermore, drugs improving the resistance to hypoxia have been investigated, such as the neurosteroid dehydroepiandrosterone sulfate (DHEAS) which has shown beneficial effects in hypoxic processes in mammals; however, at the cellular level, its exact mechanism of action has yet to be fully elucidated. Here, we used a chemical hypoxia model through sodium sulfite (SS) exposure in Caenorhabditis elegans (C. elegans), a nematode whose response to hypoxia involves pathways and cellular processes conserved in mammals, and that allows study the direct effect of DHEAS without its conversion to sex hormones. This work aimed to determine the effect of DHEAS on damage to the GABAergic system associated with SS exposure in C. elegans. Worms were subjected to nose touch response (Not Assay) and observed in epifluorescence microscopy. DHEAS decreased the shrinkage response of Not Assay and the level of damage in GABAergic neurons on SS-exposed worms. Also, the enhanced nuclear localization of DAF-16 and consequently the overexpression of chaperone HSP-16.2 by hypoxia were significantly reduced in SS + DHEAS exposed worms. As well, DHEAS increased the survival rate of worms exposed to hydrogen peroxide. These results suggest that hypoxia-caused damage over the GABAergic system was prevented at least partially by DHEAS, probably through non-genomic mechanisms that involve its antioxidant properties related to its chemical structure.

中文翻译：

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硫酸脱氢表雄酮硫酸盐的抗氧化性能可防止亚硫酸钠引起的秀丽隐杆线虫对GABA能系统的伤害。

几个病理生理过程涉及缺氧状况，神经系统也受到影响。我们假设GABA能系统特别敏感。此外，已经研究了改善对低氧耐受性的药物，例如神经甾体硫酸脱氢表雄酮硫酸盐（DHEAS），它在哺乳动物的低氧过程中显示出有益的作用；然而，在细胞水平上，其确切的作用机理尚未完全阐明。在这里，我们使用通过在亚硫酸钠（SS）曝光的化学缺氧模型秀丽隐杆线虫（秀丽隐杆线虫）线虫，其对缺氧的反应涉及哺乳动物中保守的途径和细胞过程，因此可以研究DHEAS的直接作用而无需将其转化为性激素。这项工作的目的是确定DHEAS对秀丽隐杆线虫的SS暴露相关的GABA能系统的损害的影响。蠕虫经历鼻子触觉反应（不测定），并在落射荧光显微镜下观察。DHEAS降低了Not Assay的收缩反应以及暴露于SS的蠕虫中GABA能神经元的损伤程度。同样，在暴露于SS + DHEAS的蠕虫中，DAF-16的增强的核定位以及因此由缺氧引起的伴侣HSP-16.2的过表达显着降低。同样，DHEAS可以提高接触过氧化氢的蠕虫的存活率。这些结果表明，DHEAS至少可以部分防止缺氧引起的对GABA能系统的损害，可能是通过涉及其化学结构相关的抗氧化特性的非基因组机制。