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Publications

Journal Article Epublish 1 citation

PubMed: 39468459 DOI: 10.1186/s12868-024-00902-y

ZA-II-05, a novel NMDA-receptor antagonist reverses vanadium-induced neurotoxicity in Caenorhabditis elegans (C. elegans).

BMC Neurosci 25(1):56

Authors: Amany Ladagu, Funmilayo Olopade, Paul Chazot, Taiwo Elufioye, Toan Luong, Madison Fuller, Ethan Halprin, Jessica Mckay, Zeynep Ates-Alagoz, Taidinda Gilbert, Adeboye Adejare, James Olopade

Affiliations

  • Department of Veterinary Anatomy, University of Ibadan, Ibadan, Nigeria.
  • Department of Anatomy, College of Medicine, University of Ibadan, Ibadan, Nigeria.
  • Department of Biosciences, Durham University, County Durham, DH1 3LE, UK.
  • Department of Pharmacognosy, Faculty of Pharmacy, University of Ibadan, Ibadan, Oyo, Nigeria.
  • Department of Neuroscience, College of Arts and Sciences, Saint Joseph's University, Philadelphia, PA, USA.
  • Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph's University, Philadelphia, PA, USA.
  • Department of Pharmaceutical Chemistry, Ankara University, Ankara, Turkey.
  • Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph's University, Philadelphia, PA, USA.

Abstract

INTRODUCTION

Vanadium is a widely used transition metal in industrial applications, but it also poses significant neurotoxic and environmental risks. Previous studies have shown that exposure to vanadium may lead to neurodegenerative diseases and neuropathic pain, raising concerns about its impact on human health and the ecosystem. To address vanadium neurotoxicity, through targeting NMDA glutamate and dopamine signaling, both involved in neurodegenerative disorders, shows promise. Using Caenorhabditis elegans as a model, we evaluated a novel compound with a mixed NMDA glutamate receptor-dopamine transporter pharmacology, ZA-II-05 and found it effectively ameliorated vanadium-induced neurotoxicity, suggesting a potential neuroprotective role.

METHODS

Synchronized young adult worms were assigned to four different experimental groups; Controls; 100 mM of Vanadium; Vanadium and 1 mg/ml ZA-II-05; and ZA-II-05 alone. These were examined with different markers, including DAPI, MitoTracker Green and MitoSox stains for assessment of nuclei and mitochondrial density and oxidative stress, respectively.

RESULTS

Exposure to vanadium in C. elegans resulted in decreased nuclear presence and reduction in mitochondrial content were also analyzed based on fluorescence in the pharyngeal region, signifying an increase in the production of reactive oxygen species, while vanadium co-treatment with ZA-II-05 caused a significant increase in nuclear presence and mitochondrial content.

DISCUSSION

Treatment with ZA-II-05 significantly preserved cellular integrity, exhibiting a reversal of the detrimental effects induced by vanadium by modulating and preserving the normal function of chemosensory neurons and downstream signaling pathways. This study provides valuable insights into the mechanisms of vanadium-induced neurotoxicity and offers perspectives for developing therapeutic interventions for neurodegenerative diseases related to environmental toxins.

MeSH

Receptors, N-Methyl-D-Aspartate, Dopamine, Therapeutics, Nervous System, Neurodegenerative Diseases