Transcriptomic Profiling of 6-OHDA- and Reserpine-Mediated Neurotoxicity and Neurobehavioral Change in Caenorhabditis elegans Model
DOI:
https://doi.org/10.48048/tis.2026.11920Keywords:
Transcriptome, Metascape, 6-OHDA, Reserpine, Neurotoxicity, Caenorhabditis elegansAbstract
Neurotoxic agents such as 6-hydroxydopamine (6-OHDA) and reserpine are reported to cause neurodegenerative and neuroendocrine effects, respectively. Using the Caenorhabditis elegans (C. elegans) model, this study performs comparative transcriptomic profiling to elucidate molecular pathways that contribute to their neurotoxicity. Differentially expressed genes (DEGs) were identified following 6-OHDA and reserpine exposure, with subsequent analyses for Gene Ontology (GO) and KEGG pathway enrichment. Notably, 6-OHDA mainly disrupted ribosomal/proteasomal activity and neurodegeneration-related pathways, while reserpine primarily affected the extracellular compartment, neuropeptide-based signaling, and metabolic processes. Meta-analysis of the top 3,000 DEGs, combined with comparative enrichment network analysis of the 2 neurotoxicants using Metascape, identified critical regulatory processes, including cell development, reproduction, cytoskeletal organization, cell cycle control, metabolic pathways, and post-transcriptional regulation. In addition, protein-protein interaction (PPI) network analysis revealed eight distinct Molecular Complex Detection (MCODE) modules, which correspond to biological clusters such as regulation of translation, fatty acid metabolism, glutamate/glutamine metabolism, ceramide metabolism, sphingolipid metabolism, porphyrin metabolism, and post-transcriptional regulation. Moreover, reserpine exposure altered neurobehavioral function in the ethanol avoidance assay without inducing dopaminergic (DAergic) neurodegeneration in C. elegans. Overall, these findings suggest a transcriptomic framework that reports both common and unique molecular signatures of neurotoxicant-mediated neurodegeneration and behavioral alterations. These results provide valuable insights for future studies on regulatory pathways involved in PD pathogenesis.
HIGHLIGHTS
- 6-OHDA predominantly modulated ribosomal/proteasomal activity and neurodegeneration-related processes in C. elegans.
- Reserpine primarily influenced the extracellular region, neuropeptide-mediated signaling, and metabolic processes in C. elegans.
- Overlapping enriched DEGs identified by Metascape between the 6-OHDA- and reserpine-treated groups were mainly associated with cell development, reproduction, cytoskeletal organization, cell cycle regulation, metabolic pathways, and post-transcriptional regulation.
- MCODE cluster analysis revealed metabolic modules encompassing regulation of translation, fatty acid metabolism, glutamate/glutamine metabolism, ceramide metabolism, sphingolipid metabolism, porphyrin metabolism, and post-transcriptional regulation.
- Reserpine toxicity altered dopamine-dependent behavioral function in the ethanol avoidance assay without inducing DAergic neurodegeneration in C. elegans.
GRAPHICAL ABSTRACT
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