GABAergic system’s Injuries Induced by Sodium Sulfite in Caenorhabditis elegans Were Prevented by the Anti-Oxidative Properties of Dehydroepiandrosterone Sulfate

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 dehydroepiandrosteron...

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Bibliographic Details
Published in:Neurotoxicity research 2020-08, Vol.38 (2), p.447-460
Main Authors: Gallegos-Saucedo, Manuel de Jesús, Camargo-Hernández, Gabriela, Castillo-Romero, Araceli, Ramírez-Herrera, Mario Alberto, Bañuelos-Pineda, Jacinto, Pereira-Suárez, Ana Laura, Hernández-Chávez, Abel, Hernández-Hernández, Leonardo
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Neurobiology
Neurochemistry
Neurology
Neurosciences
Original Article
Pharmacology/Toxicology
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Summary: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.
ISSN:1029-8428
1476-3524
DOI:10.1007/s12640-020-00207-y