The effect of heavy metals on differentiated neuronal and glial cells

Abstract

Heavy metal poisoning poses a serious health risk among populations worldwide. The symptoms presented by exposure are varied and depend upon the species of the metal, the age of the individual and the exposure dose. All heavy metals have debilitating effects on the CNS. Children are especially sensitive to the neurological effects due to the intense growth and activity of a developing nervous system and inadequately developed defences. The aims of this study were to determine the effects of sub-lethal concentrations of numerous heavy metals on neuronal and glial cell differentiation. Using established cellular models, the toxicity of zinc, lead, mercury, methylmercury and thimerosal were investigated using assays of cell viability and morphology on differentiating N2a and C6 cells. Initial research revealed thimerosal, methylmercury and cadmium to be the most toxic compounds tested, in terms of their ability to inhibit the outgrowth of neurites in both cell lines at sub-lethal concentrations. Although cadmium chloride showed similar patterns of toxicity to the mercury compounds, thimerosal and MeHgCl were chosen for further investigation at a molecular level. Methylmercury chloride a common environmental pollutant and thimerosal; a preservative found in many medicines, were chosen for further investigation, as previous work has demonstrated the health risks posed by the two organic mercury compounds but little is known about non-lethal changes that occur in the nervous system, especially with thimerosal