Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist

Digal Ladagu, Amany; Eniola Olopade, Funmilayo; Chazot, Paul; Oyagbemi, Ademola A.; Ohiomokhare, Samuel; Racheal Folarin, Oluwabusayo; Tashara Gilbert, Taidinda; Fuller, Madison; Luong, Toan; Adejare, Adeboye; Olopade, James O.

Abstract

Exposure to heavy metals, such as vanadium, poses an ongoing environmental and health threat, heightening the risk of neurodegenerative disorders. While several compounds have shown promise in mitigating vanadium toxicity, their efficacy is limited. Effective strategies involve targeting specific subunits of the NMDA receptor, a glutamate receptor linked to neurodegenerative conditions. The potential neuroprotective effects of ZA-II-05, an NMDA receptor antagonist, against vanadium-induced neurotoxicity were explored in this study. Organotypic rat hippocampal slices, and live mice, were used as models to comprehensively evaluate the compound’s impact. Targeted in vivo fluorescence analyses of the hippocampal slices using propidium iodide as a marker for cell death was utilized. The in vivo study involved five dams, each with eight pups, which were randomly assigned to five experimental groups (n = 8 pups). After administering treatments intraperitoneally over six months, various brain regions were assessed for neuropathologies using different immunohistochemical markers. High fluorescence intensity was observed in the hippocampal slices treated with vanadium, signifying cell death. Vanadium-exposed mice exhibited demyelination, microgliosis, and neuronal cell loss. Significantly, treatment with ZA-II-05 resulted in reduced cellular death in the rat hippocampal slices and preserved cellular integrity and morphological architecture in different anatomical regions, suggesting its potential in countering vanadium-induced neurotoxicity.

Citation

Digal Ladagu, A., Eniola Olopade, F., Chazot, P., Oyagbemi, A. A., Ohiomokhare, S., Racheal Folarin, O., …Olopade, J. O. (2023). Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist. International Journal of Molecular Sciences, 24(23), Article 16710. https://doi.org/10.3390/ijms242316710

• Journal Article Type: Article
• Acceptance Date: Nov 22, 2023
• Online Publication Date: Nov 24, 2023
• Publication Date: Dec 1, 2023
• Deposit Date: Nov 24, 2023
• Publicly Available Date: Nov 24, 2023
• Journal: International Journal of Molecular Sciences
• Print ISSN: 1661-6596
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 24
• Issue: 23
• Article Number: 16710
• DOI: https://doi.org/10.3390/ijms242316710
• Keywords: neurotoxicity, vanadium, NMDA-receptor antagonist, Alzheimer’s disease, hippocampus
• Public URL: https://durham-repository.worktribe.com/output/1948605