Neurotoxic Effect of Manganese and Vanadium Co-Exposure in Animal Models of Parkinson’s Disease

Chronic environmental exposure to mixtures of heavy metals like manganese (Mn) and vanadium (V) has been associated with Parkinson's disease (PD). We investigated the poorly understood neurotoxic effects of Mn/V co-exposure on PD-relevant behavioral phenotypes in transgenic mice expressing the human alpha-synuclein (αSyn) A53T mutant. C57BL/6 wild-type (WT) and transgenic A53T mice were intranasally co-exposed to 100 µg MnCl₂ and 75 µg V₂O₅ five times weekly for three months, simulating a 5-day workweek. This led to significant Mn/V accumulation in the brain. Exploratory locomotor activity declined significantly in Mn/V-treated A53T mice, but not in Mn/V-treated WT mice when compared to their respective vehicle controls. Motor coordination, assessed via a forced locomotor activity test, was not significantly affected in either group. In Mn/V-treated A53T mice, olfactory deficits were present, but not in Mn/V-treated WT mice. Behavioral despair, assessed by tail suspension and forced swim tests, was not induced by Mn/V co-exposure in any group compared to their vehicle controls. Mn/V-treated A53T mice exhibited anxiety-like behavior and hyperactivity. These findings suggest that Mn/V co-exposure exacerbates neurotoxic effects in A53T mice, with a more pronounced effect in males, providing insight into the role of metal mixture exposure in environmentally linked Parkinsonism.