Nickel-induced neurodegeneration in the hippocampus, striatum and cortex; an ultrastructural insight, and the role of caspase-3 and α-synuclein

Human overexposure to nickel (Ni) emanating from the increasing application of Ni compounds in modern technology is a major public health concern. Nickel has been shown to be teratogenic, immunotoxic, genotoxic and carcinogenic. The current knowledge on Ni neurotoxicity is still relatively limited. We have previously demonstrated that Ni treatment alters cognitive and locomotor behaviors, induces oxidative stress and neurodegeneration in brains of rats. In this study, we examine the ultrastructural changes to neurons in the hippocampus, striatum and cortex of the brain following Ni treatment, as well as attempt to delineate the roles for caspase-3 and α-synuclein in Ni-induced neurodegeneration. Rats were treated with either saline, 10 or 20 mg/kg of nickel chloride for 4 weeks via oral gavage. Electron microscopy analysis revealed ultrastructural alterations in neurons of the hippocampus, striatum and cortex following Ni treatment. Mitochondria structural integrity within neurons were markedly compromised. We also detected elevated caspase-3 activity in hippocampus and striatum, as well as overexpression of α-synuclein in the cortex following Ni treatment. Our study demonstrates that mitochondria are a key target in Ni-induced neurodegeneration. Additionally, we implicate apoptotic pathway via caspase-3 action as the executioner and perturbation of α-synuclein expression in Ni-induced neurodegeneration.