Manganese toxicity in serumless dissociated mesencephalic and striatal primary culture

Abstract

Exposure to elevated levels of Manganese (Mn) can result in an irreversible brain disease characterized by extrapyramidal signs and symptoms resembling Parkinson's disease. To identify the neuronal target of Mn neurotoxicity, MnCl2 was added to serumless dissociated mesencephalic-striatal cultures from rat embryo on day 4 in vitro. High affinity 3H-dopamine (DA) and 14C-GABA uptakes were assessed as specific functional markers of DAergic and GABAergic cell viability, respectively. After 60-min exposure, MnCl2 at 0-200 microM did not modify the morphologic appearance of the cultures, specific DA and GABA uptakes, or the number of DA neurons visualized by immuno-cytochemical staining with tyrosine hydroxylase. In contrast, culture exposure to 20 microM MnCl2 for 24 h selectively reduced specific GABA uptake without affecting specific DA uptake or the number of DA neurons. The exposure to a higher MnCl2 concentration was accompanied by signs of general toxicity. Striatal GABA neurons seemed to be more susceptible to Mn toxicity than mesencephalic GABA neurons. Overall, our data suggest that striatal neurons rather than mesencephalic DA neurons may be the main target of Mn neurotoxicity.