Effects of in-vivo Vanadium-Induced Neurotoxicity and Withdrawal on Three Consecutive Generations of Mice Brains: A Neurobehavioural and Histo-Immunohistochemical Study

Abstract

Heavy metals exposure causes multi-systemic pathologies in biological systems. Due to their genotoxic effects, some of these anomalies have been reported to transcend to unexposed generations. Vanadi-um, a transition metal, crosses the blood brain barrier, causing neuroinflammatory and demyelinating lesions with neurobehavioural inadequacies in exposed subjects. There are however scarce scientific information on vanadium neurotoxicity over generations of exposed subjects. This study explored the effects of vanadium exposure on the body weight, neurobehavioural (open field and negative geotaxis tests) and neurohistological changes (Purkinje cell, astroglial and myelin histoarchitecture) in three consecutive generations – two exposed generations (G1 and G2) and one withdrawal generation (G3), of mice. Neonatal pups of BALB/c mice in G1 and G2, were treated with sodium metavanadate every 48 h, first via lactation from post natal day (PND) 1-14, and later intraperitoneally (PND 15-21) for males; PND 15-45 for female pups till they were mated with unexposed males. The G3 pups were not treated with sodium metavanadate. The vanadium treated pups had irregular body weight gain. In all the studied generations (G1-3), there were reduced locomotor and exploratory activities, and diminished motor and vestibular function compared to the controls. Furthermore, there was multilayering and pyknosis of the cerebellar Purkinje cells, moderate to marked astrogliosis and generalized demyelination in the corpus callosum, hippocampus (CA1-4 and the dentate gyrus), cerebral cortex, thalamus and cerebellum. This study revealed that effects of vanadium exposure including neurobehavioural anomalies, astrogliosis, demyelination and cerebellar Purkinje cell pathology can persist across multiple generations, including generation not initially exposed