Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist
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 su...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-11-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/23/16710 |
| _version_ | 1797400148190429184 |
|---|---|
| author | Amany Digal Ladagu Funmilayo Eniola Olopade Paul Chazot Ademola A. Oyagbemi Samuel Ohiomokhare Oluwabusayo Racheal Folarin Taidinda Tashara Gilbert Madison Fuller Toan Luong Adeboye Adejare James O. Olopade |
| author_facet | Amany Digal Ladagu Funmilayo Eniola Olopade Paul Chazot Ademola A. Oyagbemi Samuel Ohiomokhare Oluwabusayo Racheal Folarin Taidinda Tashara Gilbert Madison Fuller Toan Luong Adeboye Adejare James O. Olopade |
| author_sort | Amany Digal Ladagu |
| collection | DOAJ |
| description | 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 (<i>n</i> = 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. |
| first_indexed | 2024-03-09T01:50:20Z |
| format | Article |
| id | doaj.art-e470fd4256d14a10b2388685f7a0cd61 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T01:50:20Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e470fd4256d14a10b2388685f7a0cd612023-12-08T15:16:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124231671010.3390/ijms242316710Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor AntagonistAmany Digal Ladagu0Funmilayo Eniola Olopade1Paul Chazot2Ademola A. Oyagbemi3Samuel Ohiomokhare4Oluwabusayo Racheal Folarin5Taidinda Tashara Gilbert6Madison Fuller7Toan Luong8Adeboye Adejare9James O. Olopade10Department of Veterinary Anatomy, University of Ibadan, Ibadan 200284, NigeriaDepartment of Anatomy, College of Medicine, University of Ibadan, Ibadan 200284, NigeriaDepartment of Biosciences, Durham University, County Durham DH1 3LE, UKDepartment of Veterinary Physiology and Biochemistry, Faculty of Veterinary Medicine, University of Ibadan, Ibadan 200284, NigeriaDepartment of Biosciences, Durham University, County Durham DH1 3LE, UKDepartment of Veterinary Anatomy, University of Ibadan, Ibadan 200284, NigeriaDepartment of Veterinary Anatomy, University of Ibadan, Ibadan 200284, NigeriaDepartment of Neuroscience, College of Arts and Sciences, Saint Joseph’s University, Philadelphia, PA 19131, USADepartment of Neuroscience, College of Arts and Sciences, Saint Joseph’s University, Philadelphia, PA 19131, USADepartment of Pharmaceutical Sciences, Philadelphia College of Pharmacy, Saint Joseph’s University, Philadelphia, PA 19131, USADepartment of Veterinary Anatomy, University of Ibadan, Ibadan 200284, NigeriaExposure 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 (<i>n</i> = 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.https://www.mdpi.com/1422-0067/24/23/16710Alzheimer’s diseasevanadiumNMDA-receptor antagonistneurotoxicityhippocampus |
| spellingShingle | Amany Digal Ladagu Funmilayo Eniola Olopade Paul Chazot Ademola A. Oyagbemi Samuel Ohiomokhare Oluwabusayo Racheal Folarin Taidinda Tashara Gilbert Madison Fuller Toan Luong Adeboye Adejare James O. Olopade 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 Alzheimer’s disease vanadium NMDA-receptor antagonist neurotoxicity hippocampus |
| title | Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist |
| title_full | Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist |
| title_fullStr | Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist |
| title_full_unstemmed | Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist |
| title_short | Attenuation of Vanadium-Induced Neurotoxicity in Rat Hippocampal Slices (In Vitro) and Mice (In Vivo) by ZA-II-05, a Novel NMDA-Receptor Antagonist |
| title_sort | attenuation of vanadium induced neurotoxicity in rat hippocampal slices in vitro and mice in vivo by za ii 05 a novel nmda receptor antagonist |
| topic | Alzheimer’s disease vanadium NMDA-receptor antagonist neurotoxicity hippocampus |
| url | https://www.mdpi.com/1422-0067/24/23/16710 |
| work_keys_str_mv | AT amanydigalladagu attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT funmilayoeniolaolopade attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT paulchazot attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT ademolaaoyagbemi attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT samuelohiomokhare attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT oluwabusayorachealfolarin attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT taidindatasharagilbert attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT madisonfuller attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT toanluong attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT adeboyeadejare attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist AT jamesoolopade attenuationofvanadiuminducedneurotoxicityinrathippocampalslicesinvitroandmiceinvivobyzaii05anovelnmdareceptorantagonist |