دورية أكاديمية
Novel NMDA-receptor antagonists ameliorate vanadium neurotoxicity.
| العنوان: | Novel NMDA-receptor antagonists ameliorate vanadium neurotoxicity. |
|---|---|
| المؤلفون: | Ladagu AD; Department of Veterinary Anatomy, University of Ibadan, Oyo, Nigeria., Olopade FE; Department of Anatomy, University of Ibadan, Oyo, Nigeria., Folarin OR; Department of Veterinary Anatomy, University of Ibadan, Oyo, Nigeria., Elufioye TO; Department of Pharmacognosy, University of Ibadan, Oyo, Nigeria., Wallach JV; Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA., Dybek MB; Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA., Olopade JO; Department of Veterinary Anatomy, University of Ibadan, Oyo, Nigeria. jkayodeolopade@yahoo.com., Adejare A; Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA. |
| المصدر: | Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2020 Sep; Vol. 393 (9), pp. 1729-1738. Date of Electronic Publication: 2020 May 09. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0326264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1912 (Electronic) Linking ISSN: 00281298 NLM ISO Abbreviation: Naunyn Schmiedebergs Arch Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Berlin, New York, Springer Verlag. |
| مواضيع طبية MeSH: | Nerve Degeneration*, Excitatory Amino Acid Antagonists/*pharmacology , Neurotoxicity Syndromes/*prevention & control , Purkinje Cells/*drug effects , Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors, Animals ; Astrocytes/drug effects ; Astrocytes/metabolism ; Astrocytes/pathology ; Calbindins/metabolism ; Cell Death/drug effects ; Disease Models, Animal ; Glial Fibrillary Acidic Protein/metabolism ; Mice ; Microglia/drug effects ; Microglia/metabolism ; Microglia/pathology ; Neurotoxicity Syndromes/etiology ; Neurotoxicity Syndromes/metabolism ; Neurotoxicity Syndromes/pathology ; Purkinje Cells/metabolism ; Purkinje Cells/pathology ; Receptors, N-Methyl-D-Aspartate/metabolism ; Vanadates |
| مستخلص: | Various NMDA-receptor antagonists have been investigated for their therapeutic potential in Alzheimer's disease with memantine shown to be safe and with relative efficacy. There is, however, need to develop novel drugs to counter tolerance and with better efficacy in ameliorating neurodegeneration. We have shown neurodegeneration in different models of vanadium-exposed mice. This study was designed to evaluate and ascertain the potency of three novel NMDA-receptor antagonists (Compounds A, B and C) to ameliorate neurodegeneration in vanadium-exposed mice. One-month-old mice (n = 6) received sterile water (control) and another group (n = 6) was treated with vanadium (3 mg/kg sodium metavanadate) intraperitoneally for 1 month. Three other groups (n = 6) received vanadium and compounds A, B and C (4.35 mg/kg, 30 mg/kg and 100 mg/kg, respectively) simultaneously for the same period. Assessment of pathologies and neurodegeneration in different brain regions was done to test the ameliorative effects of the 3 antagonists using different immunohistochemical markers. Vanadium exposure resulted in reduced calbindin expression and pyknosis of Purkinje cells, cell loss and destruction of apical dendrites with greater percentage of cytoplasmic vacuolations, morphological alterations characterized by cell clustering and multiple layering patterns in the Purkinje cell layer. In addition, the observed degeneration included demyelination, increased GFAP-immunoreactive cells and microgliosis. Simultaneous administration of the compounds to vanadium-exposed mice resulted in the preservation of cellular integrity in the same anatomical regions and restoration of the cells' vitality with reduced astroglial and microglial activation. |
| فهرسة مساهمة: | Keywords: Alzheimer’s disease; Compounds; NMDA-receptor antagonist; Neurodegeneration; Purkinje cells; Vanadium |
| المشرفين على المادة: | 0 (Calbindins) 0 (Excitatory Amino Acid Antagonists) 0 (Glial Fibrillary Acidic Protein) 0 (Receptors, N-Methyl-D-Aspartate) 0 (glial fibrillary astrocytic protein, mouse) 3WHH0066W5 (Vanadates) |
| تواريخ الأحداث: | Date Created: 20200511 Date Completed: 20210728 Latest Revision: 20210728 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1007/s00210-020-01882-6 |
| PMID: | 32388602 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1432-1912 |
|---|---|
| DOI: | 10.1007/s00210-020-01882-6 |