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

## TL;DR

This study uses C. elegans and a chemical agent to model developmental delays and test supplements that may help alleviate symptoms similar to autism.

## Contribution

A new model using C. elegans and DTT is proposed, along with testing supplements to address developmental and stress-related impairments.

## Key findings

- The supplement and its components partially reversed developmental delays and GABAergic impairments caused by DTT.
- Vitamins B9, B12, and the supplement offered partial protection against oxidative stress from Paraquat.
- In silico analysis linked supplement components to ASD-related pathways like immunomodulation and synaptic pruning.

## Abstract

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.