Nutritional Supplementation Benefits in Caenorhabditis elegans under Developmental Disruption and Stress Conditions

Autism spectrum disorder (ASD) is a developmental and neurological condition that impacts an individual's behavior, communication, social interaction, and learning abilities. This disease is complex and involves different mechanisms, and therefore, modeling is a major challenge. Some features can be reproduced in different animal models to investigate therapeutic approaches. Here, we proposed a new simple model to induce development delay by using the nematode Caenorhabditis elegans and dithiothreitol (DTT) as a chemical agent. In order to investigate a complementary treatment, a commercial supplement and its isolated components (vit. B12, B1, B6, and B9), curcumin, and palmitoylethanolamide (PEA) were used to revert the oxidative stress, development impairments, and metabolomic changes caused by DTT. Furthermore, computational tools predicted pharmacokinetic properties (SwissADME) and possible pathways (enrichment analysis) linked to ASD, an important neurodevelopmental disorder. The supplement and its components (curcumin, PEA, vit. B12, B6, and B9) partially alleviated the delay in larval progression and completely recovered the GABAergic neurodevelopmental impairments (supplement, curcumin, vit. B6, B9, and B12) caused by DDT. Vitamin B9, B12, and supplement partially protected mortality against the oxidative stressor Paraquat. Curcumin, vit. B1, B6, and supplement showed potential protection against coexposure to DTT by reducing DAF-16 migration to the nucleus compared to DTT. Vitamins B1, B9, and B12 coexposure to DTT positively modulated SOD-3 expression. Amino acids, carnitines, and lipids revealed by LC-MS analysis enabled group differentiation and pathway analysis, indicating potential signaling molecules. In silico analysis predicted that these components may interact with pathways linked to ASD pathogenesis such as immunomodulation, synaptic pruning, and complex behavior regulation. Our data indicate that DTT is a good chemical model to induce developmental disorders and that the supplement, with all its components associated, is a promising therapy to be investigated in ASD.