Abstract
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.
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Acknowledgments
The authors thank Annie Riera-Leal (CUCS-Universidad de Guadalajara) for technical assistance. We are grateful to the C. elegans Genetics Center, which is supported by NIH’s National Center for Research Resources, for providing strains.
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MJGS was supported by a fellowship (373878) from the CONACyT-Mexico. This work was supported in part by CONACyT (Postdoctoral Grant No. 41133) and a grant (2.5.9.1) from PRO-SNI-UdeG (2019) to GCH. MJGS was supported by a fellowship (373878) from the CONACyT-Mexico.
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Gallegos-Saucedo, M.d., Camargo-Hernández, G., Castillo-Romero, A. et al. GABAergic system’s Injuries Induced by Sodium Sulfite in Caenorhabditis elegans Were Prevented by the Anti-Oxidative Properties of Dehydroepiandrosterone Sulfate. Neurotox Res 38, 447–460 (2020). https://doi.org/10.1007/s12640-020-00207-y
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DOI: https://doi.org/10.1007/s12640-020-00207-y