Novel NMDA-receptor antagonists ameliorate vanadium neurotoxicity
- PDF / 2,342,879 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 24 Downloads / 202 Views
ORIGINAL ARTICLE
Novel NMDA-receptor antagonists ameliorate vanadium neurotoxicity A. D. Ladagu 1 & F. E. Olopade 2 A. Adejare 4
&
O. R. Folarin 1 & T. O. Elufioye 3 & J. V. Wallach 4 & M. B. Dybek 4 & J. O. Olopade 1
&
Received: 10 January 2020 / Accepted: 22 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 vanadiumexposed 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. Keywords Alzheimer’s disease . Vanadium . NMDA-receptor antagonist . Neurodegeneration . Purkinje cells . Compounds
Introduction Vanadium is a transition metal (atomic number 23) which is widely distributed in nature and extensively used in the chemical industry (Cui et al. 2015; Ray et al. 2006). It exists in water, rocks and soil in low concentrations and relatively high concentrations in oil and coal deposits (Zhang et al. 2001).
* J. O. Olopade [email protected] 1
Department of Veterinary Anatomy, University of Ibadan, Oyo, Nigeria
2
Department of Anatomy, University of Ibadan, Oyo, Nigeria
3
Department of Pharmacognosy, University of Ibadan, Oyo, Nigeria
4
Department of Pharmaceutical Sciences, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, PA, USA
Vanadium has been shown to have neurotoxic effects (Folarin et al. 2017a; Garcia et al. 2005), and as a vanadate anion, it crosses the blood brain barrier, which leads to
Data Loading...
