Cerebellar and Olfactory Bulb Perturbations Induced by Vanadium Neurotoxicity in the African Giant Rat (Cricetomys gambianus, Waterhouse).

The African giant rat, AGR (Cricetomys gambianus) is a unique rodent known for its keen sense of smell which has enabled its use in the diagnosis of tuberculosis and demining activities in war torn countries. This keen sense of smell and the ability to navigate tight spaces are skills modulated by the olfactory bulb and cerebellum. While the brain is generally susceptible to environmental pollutants such as heavy metals, vanadium has predilection for these two brain regions. This work was thus designed to investigate the probable neurotoxic effect of vanadium on the neuronal cytoarchitecture of the cerebellum and olfactory bulb in this rodent. To achieve this, twelve adults male AGRs were divided into two groups (vanadium and control groups) and were given intraperitoneal injections of 3mg/kg body weight sodium metavanadate and normal saline respectively for 14 days. After which they were sacrificed, and brains harvested for histological investigations using Nissl and Golgi staining techniques. Results from our experiment revealed Purkinje cell degeneration and pyknosis as revealed by a lower intact-pyknotic cell (I-P) ratio, higher pyknotic Purkinje cell density and poor dendritic arborizations in the molecular layer of the cerebellum in the vanadium treated group. In the olfactory bulb, neuronal loss in the glomerular layer was observed as shrunken glomeruli. These neuronal changes have been linked to deficits in motor function and disruption of odor transduction in the olfactory bulb. This work has further demonstrated the neurotoxic effects of vanadium on the cerebellum and olfactory bulb of the AGR and the likely threat it may pose to the translational potentials of this rodent. We therefore propose the use of this rodent as a suitable model for better understanding vanadium induced olfactory and cerebellar dysfunctions.

Neurobehavioural and Histological Study of the Effects of Low-Dose and High-Dose Vanadium in Brain, Liver and Kidney of Mice.

Vanadium is a ubiquitous transition metal that has been generating contrasting research interest. Therapeutically, vanadium possess antidiabetic, antitumor, antiparasitic and even neuroprotective activities. On the flip side, vanadium has been reported to cause multisystemic toxicities with a strong predilection for the nervous system. Despite several reports on potential benefits of low-dose vanadium (LDV) and toxic effects of high-dose vanadium (HDV), there are no comparative studies done thus far. This study therefore explored the comparative effects of LDV and HDV exposure in mice during postnatal development. A total of nine (9) nursing mice were used in this study; with three nursing mice and their pups (n = 12 pups per group) randomly assigned to each of the three test groups. The nursing dam were given intraperitoneal (i.p) injection of vanadium at 0.15mg/kg and 3mg/kg for LDV and HDV respectively, and subseqently to the pups from postnatal day (PND) 15 till sacrifice on PND 90. We discovered that neurodevelopmental motor function test of mice-pups exposed to LDV here showed improved motor development, muscular strength and memory capacities whereas HDV led to motor function impairment, reduced muscular strength and memory capacities.  LDV-exposed mice showed mild histological lesions in cerebral cortex whereas high-dose showed distinct histological lesions in different parts of the brain ranging from cerebellar Purkinje neuronal pathology (central chromatolysis), pyramidal neuronal loss in CA1 region, architectural distortion as well as fewer neurons in olfactory bulb. We saw mild lesions with LDV in both liver and kidney, however, with HDV exposure, there was diffuse hepatocellular vacuolar degeneration and congestion of blood vessels in liver, shrinkage of renal glomerulus and degenerated epithelial cells of kidney. Conclusively, beneficial effect of vanadium is proven as it facilitated body weight gain which translate in organ weight at low-dose, while high-dose caused decreased neurobehaviour and histological lesions.

Morphological Characterization of the Developing Greater Cane Rat (Thryonomys swinderianus) Brain.

Developmental mode along the altricial-precocial spectrum is well known to be influenced by brain development and maturation. The greater cane rat (GCR) is an indigenous precocial African rodent with uncommon phenotypes and life traits. This study was therefore designed to characterize and describe distinctive external developmental features in the prenatal GCR brain across the entire gestational length using the emergence and differentiation of external features of the brain vesicles. Four gross morphometric brain parameters (weight, length, width, and height) were evaluated and expressed as mean ± SEM. Relationship between all brain morphometrics and gestation length were analyzed using one-way ANOVA and linear regression. Developmental milestones in the prenatal GCR were then compared with closely related precocial mammals. The earliest time point with gross observable features in the prenatal GCR brain was at gestation day (GD) 60. The period with the most remarkable gross developmental features was noted between GD80 and GD100. Some of these gross features include differentiation of the cerebellar plate into vermis and lateral lobes, emergence of the piriform lobes, mammillary bodies, colliculi bodies, cerebral peduncles, and primordial pons. By GD130, most gross topographic neural features were already established. Cerebellar lobation and patterning at GD130 were the last recognizable gross developmental features noticed in the prenatal GCR brain. This coincided with the time of first eye opening in the GCR fetus. The developmental pattern observed in the prenatal GCR brain is similar to those noted in precocial rodent like the guinea pig. However, the onset of these milestones was delayed, and their duration was relatively shorter in the GCR. This study provides a frame of baseline reference of morphological brain features in the GCR embryos and fetuses that will be useful for fetal age estimation, for home grown neurodevelopmental and eco-toxicological studies, as this rodent is being proposed as a research model.

The Pathopharmacological Interplay between Vanadium and Iron in Parkinson's Disease Models.

Parkinson's disease (PD) pathology is characterised by distinct types of cellular defects, notably associated with oxidative damage and mitochondria dysfunction, leading to the selective loss of dopaminergic neurons in the brain's substantia nigra pars compacta (SNpc). Exposure to some environmental toxicants and heavy metals has been associated with PD pathogenesis. Raised iron levels have also been consistently observed in the nigrostriatal pathway of PD cases. This study explored, for the first time, the effects of an exogenous environmental heavy metal (vanadium) and its interaction with iron, focusing on the subtoxic effects of these metals on PD-like oxidative stress phenotypes in Catecholaminergic a-differentiated (CAD) cells and PTEN-induced kinase 1 (PINK-1)B9Drosophila melanogaster models of PD. We found that undifferentiated CAD cells were more susceptible to vanadium exposure than differentiated cells, and this susceptibility was modulated by iron. In PINK-1 flies, the exposure to chronic low doses of vanadium exacerbated the existing motor deficits, reduced survival, and increased the production of reactive oxygen species (ROS). Both Aloysia citrodora Paláu, a natural iron chelator, and Deferoxamine Mesylate (DFO), a synthetic iron chelator, significantly protected against the PD-like phenotypes in both models. These results favour the case for iron-chelation therapy as a viable option for the symptomatic treatment of PD.

Trends in vanadium neurotoxicity.

Vanadium, atomic number 23, is a transition metal widely distributed in nature. It is a major contaminant of fossil fuels and is widely used in industry as catalysts, in welding, and making steel alloys. Over the years, vanadium compounds have been generating interests due to their use as therapeutic agents in the control of diabetes, tuberculosis, and some neoplasms. However, the toxicity of vanadium compounds is well documented in literature with occupational exposure of workers in vanadium allied industries, environmental pollution from combustion of fossil fuels and industrial exhausts receiving concerns as major sources of toxicity and a likely predisposing factor in the aetiopathogenesis of neurodegenerative diseases. A lot has been done to understand the neurotoxic effects of vanadium, its mechanisms of action and possible antidotes. Sequel to our review of the subject in 2011, this present review is to detail the recent insights gained in vanadium neurotoxicity.