The Caenorhabditis elegans neuroendocrine system and their modulators: An overview.

In this review we seek to systematically bring what has been published in the literature about the nervous system, endocrine system, neuroendocrine relationships, neuroendocrine modulations and endocrine disruptors in the alternative model Caenorhabditis elegans. The serotonergic, dopaminergic, GABAergic and glutamatergic neurotransmitters are related to the modulation of the neuroendocrine axis, leading to the activation or inhibition of several processes that occur in the worm through distinct and interconnected pathways. Furthermore, this review addresses the gut-neuronal axis as it has been revealed in recent years that gut microbiota impacts on neuronal functions. This review also approaches xenobiotics that can positively or negatively impact the neuroendocrine system in C. elegans as in mammals, which allows the application of this nematode to screen new drugs and to identify toxicants that are endocrine disruptors.

The impact of manganese on neurotransmitter systems.

BACKGROUND: Manganese (Mn) is a metal ubiquitously present in nature and essential for many living organisms. As a trace element, it is required in small amounts for the proper functioning of several important enzymes, and reports of Mn deficiency are indeed rare. METHODS: This mini-review will cover aspects of Mn toxicokinetics and its impact on brain neurotransmission, as well as its Janus-faced effects on humans and other animal's health. RESULTS: The estimated safe upper limit of intracellular Mn for physiological function is in anarrow range of 20-53 µM.Therefore, intake of higher levels of Mn and the outcomes, especially to the nervous system, have been well documented. CONCLUSION: The metal affects mostly the brain by accumulating in specific areas, altering cognitive functions and locomotion, thus severely impacting the health of the exposed organisms.

Butiá fruit extract (Butia eriospatha) protects against oxidative damage and increases lifespan on Caenorhabditis elegans.

Butiá (Butia eriospatha) is a fruit of a palm tree belonging to the family Arecaceae, native to South America. The aim of this study was to evaluate the antioxidant potential of butiá extract using Caenorhabditis elegans as animal model. Initially, we performed survival experiments, reproduction, resistance to oxidative stress (post or pre-treatment with paraquat or hydrogen peroxide), longevity, superoxide dismutase, and catalase GFP reporters' expression. We observed that butiá extract did not affect the worms' survival. Similarly, egg laying also showed no significant difference between treatments. None of the extract concentrations tested was able to significantly protect or reverse paraquat-induced oxidative stress. However, they were able to reverse the oxidative damage induced by hydrogen peroxide. In addition, butiá extract increased C. elegans lifespan under stress and not per se. Our results demonstrate that the Butiá is able to extend the lifespan of the nematode C. elegans and that this effect may be mediated by an induced resistance to oxidative stress. PRACTICAL APPLICATIONS: The practical applications of this research are to expand and bring scientific knowledge to the population about the benefits of the consumption of this native fruit from the southern region of Brazil. Many fruits and other plant foods are consumed and spread with benefits without proper scientific proof of these benefits. This fruit is widely cultivated and its production and consumption can be expanded from these results. Still, we point out that this is the first time that the benefits of this fruit are studied.

Organoselenotriazoles attenuate oxidative damage induced by mitochondrial dysfunction in mev-1 Caenorhabditis elegans mutants.

Organic selenium compounds have several pharmacological activities already described, as anti-inflammatory and antitumor activities, which have been attributed to their antioxidant effects. Because they are promising in pharmacology, the synthesis of these compounds has increased significantly. As many new molecules are synthesized the use of a simple model like Caenorhabditis elegans is highly advantageous for initial evaluation of the toxicity and therapeutic potential of these molecules. The objective of this study was to evaluate the toxicity and antioxidant capacity of a series of selenotriazoles compounds in C. elegans. The animals were exposed to the compounds in liquid medium for only 30 min at the first larval stage (L1). The compounds had no toxic effects at the concentrations tested. Treatment with selenotriazoles (10 µM) partially reversed the stress induced by the pesticide paraquat (1 mM). Se-Tz Ia compound partially increased the survival of worms treated with H2O2 (0.5 mM). The compounds also increased the longevity of mev-1 mutants, which have a reduced life span by the production of excessive reactive oxygen species (ROS) in the mitochondria caused by a mutation in complex II of the electron transport chain. In addition, the compounds reduced the levels of ROS determined by the fluorescent probe DCF-DA as well as also reduced catalase enzyme activity in these animals. Based on the results found, it is possible to conclude that the compounds have antioxidant activity mainly in oxidative stress condition generated by a mitochondrial dysfunction in C. elegans.

Purple pitanga fruit (Eugenia uniflora L.) protects against oxidative stress and increase the lifespan in Caenorhabditis elegans via the DAF-16/FOXO pathway.

Pitanga, a fruit of the pitangueira tree (Eugenia uniflora L.), is native to Brazil and has a high antioxidant capacity due to the elevated amount of anthocyanins. The present study aimed to investigate the chemical composition of the purple pitanga fruit and to evaluate its antioxidant effect in the nematode Caenorhabditis elegans. We observed that the ethanolic extract of purple pitanga did not cause any toxic effects but notably increased worm lifespan. The extract improved the survival, reproduction and lifespan of the worms in pre- and post-exposure to stressors H2O2 and juglone, as well as improved the lifespan of the oxidative stress hypersensitive strain mev-1. Notably, PPE extract decreased reactive oxygen species by DCF-DA probe and protein carbonyl content from worms stressed with H2O2. The extract also affected the expression of superoxide dismutase SOD-3 and heat shock protein HSP-16.2 levels, daf 16 target genes that modulate lifespan and antioxidant metabolism. In addition, we demonstrate that these effects are dependent on DAF-16, as PPE extract did not provide protection in daf-16 mutants. Therefore, these results suggest that PPE significantly protected against oxidative stress modulating daf-16 target genes.

Direct synthesis of 4-organylsulfenyl-7-chloro quinolines and their toxicological and pharmacological activities in Caenorhabditis elegans.

We describe herein our results on the synthesis and biological properties in Caenorhabditis elegans of a range of 4-organylsulfenyl-7-chloroquinolines. This class of compounds have been easily synthesized in high yields by direct reaction of 4,7-dichloroquinoline with organylthiols using DMSO as solvent at room temperature under air atmosphere and tolerates a range of substituents in the organylsulfenyl moiety. We have performed a toxicological and pharmacological screening of the synthesized 4-organylsulfenyl-7-chloroquinolines in vivo in C. elegans acutely exposed to these compounds, under per se and stress conditions. Hence, we determined the lethal dose 50% (LD50), in order to choose a nonlethal concentration (10 µM) and verified that at that concentration some of the compounds depicted protective action against the induced damage inflicted by paraquat, a superoxide generator. Two compounds (3c and 3h) reduced the toxicity inflicted by paraquat above survival, reproduction and longevity of the worms, at least in part, by reducing the reactive oxygen species (ROS) generated by the toxicant exposure. Besides, these compounds increased the quantities of superoxide dismutase (SOD-3::GFP) and catalase (CTL-1,2,3::GFP), antioxidant enzymes. We concluded that the protective effects of the compounds observed in this study might have been a hormetic response dependent of the transcriptional factor DAF-16/FOXO, causing a non-lethal oxidative stress that protects against the subsequently damage induced by paraquat.

Seleno- and telluro-xylofuranosides attenuate Mn-induced toxicity in C. elegans via the DAF-16/FOXO pathway.

Organochalcogens are promising pharmacological agents that possess significant biological activities. Nevertheless, because of the complexity of mammalian models, it has been difficult to determine the molecular pathways and specific proteins that are modulated in response to treatments with these compounds. The nematode worm Caenorhabditis elegans is an alternative experimental model that affords easy genetic manipulations, green fluorescent protein tagging and in vivo live analysis of toxicity. Abundant evidence points to oxidative stress in mediating manganese (Mn)-induced toxicity. In this study we challenged worms with Mn, and investigated the efficacy of inedited selenium- and tellurium-xylofuranosides in reversing and/or protecting the worms from Mn-induced toxicity. In addition, we investigated their putative mechanism of action. First, we determined the lethal dose 50% (LD50) and the effects of the xylofuranosides on various toxic parameters. This was followed by studies on the ability of xylofuranosides to afford protection against Mn-induced toxicity. Both Se- and Te-xylofuranosides increased the expression of superoxide dismutase (SOD-3). Furthermore, we observed that the xylofuranosides induced nuclear translocation of the transcription factor DAF-16/FOXO, which in the worm is known to regulate stress responsiveness, aging and metabolism. These findings suggest that xylofuranosides attenuate toxicity Mn-induced, by regulating the DAF-16/FOXO signaling pathway.