ZA-II-05, a novel NMDA-receptor antagonist reverses vanadium-induced neurotoxicity in Caenorhabditis elegans (C. elegans).
Animals
Caenorhabditis elegans
/ drug effects
Receptors, N-Methyl-D-Aspartate
/ metabolism
Vanadium
/ pharmacology
Neurotoxicity Syndromes
/ drug therapy
Neuroprotective Agents
/ pharmacology
Oxidative Stress
/ drug effects
Excitatory Amino Acid Antagonists
/ pharmacology
Mitochondria
/ drug effects
Caenorhabditis
elegans
NMDA receptor antagonist
Neurodegenerative diseases
Neurotoxicity
Vanadium
Journal
BMC neuroscience
ISSN: 1471-2202
Titre abrégé: BMC Neurosci
Pays: England
ID NLM: 100966986
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
31
05
2024
accepted:
25
09
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 39468459
doi: 10.1186/s12868-024-00902-y
pii: 10.1186/s12868-024-00902-y
doi:
Substances chimiques
Receptors, N-Methyl-D-Aspartate
0
Vanadium
00J9J9XKDE
Neuroprotective Agents
0
Excitatory Amino Acid Antagonists
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
56Informations de copyright
© 2024. The Author(s).
Références
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