Prolactin is a peripheral marker of manganese neurotoxicity

Excessive exposure to Mn induces neurotoxicity, referred to as manganism. Exposure assessment relies on Mn blood and urine analyses, both of which show poor correlation to exposure. Accordingly, there is a critical need for better surrogate biomarkers of Mn exposure. The aim of this study was to examine the relationship between Mn exposure and early indicators of neurotoxicity, with particular emphasis on peripheral biomarkers. Male Wistar rats (180-200 g) were injected intraperitoneally with 4 or 8 doses of Mn (10 mg/kg). Mn exposure was evaluated by analysis of Mn levels in brain and blood along with biochemical end-points (see below). Results: Brain Mn levels were significantly increased both after 4 and 8 doses of Mn compared with controls (p < 0.001). Blood levels failed to reflect a dose-dependent increase in brain Mn, with only the 8-dose-treated group showing significant differences (p < 0.001). Brain glutathione (GSH) levels were significantly decreased in the 8-dose-treated animals (p < 0.001). A significant and dose-dependent increase in prolactin levels was found for both treated groups (p < 0.001) compared to controls. In addition, a decrease in motor activity was observed in the 8-dose-treated group compared to controls. Conclusions: (1) The present study demonstrates that peripheral blood level is a poor indicator of Mn brain accumulation and exposure; (2) Mn reduces GSH brain levels, likely reflecting oxidative stress; (3) Mn increases blood prolactin levels, indicating changes in the integrity of the dopaminergic system. Taken together these results suggest that peripheral prolactin levels may serve as reliable predictive biomarkers of Mn neurotoxicity.