Effects of p-Aminosalicylic acid on the neurotoxicity of manganese on the dopaminergic innervation of the cilia of the lateral cells of the gill of the bivalve mollusc, Crassostrea virginica.

The lateral cilia of the gill of Crassostrea virginica are controlled by a dopaminergic-serotonergic innervation. Dopamine is the neurotransmitter causing cilio-inhibition. High levels of manganese are neurotoxic to people, causing Manganism, a Parkinson-like disease. Clinical interventions for Manganism have not been very successful. Recently, p-Aminosalicylic acid (PAS) was reported as an effective treatment of severe Manganism in humans; however, its mechanism of action is unknown. Previously, we reported that manganese treatments caused disruption of the dopaminergic innervation of gill of C. virginica. Here we compared the effects of manganese on gill innervation in the presence of PAS, EDTA or Acetylsalicylic acid (ASA), and examined whether co-treating animals with PAS could block the deleterious effects of manganese on the oyster's dopaminergic innervation of the gill. Beating rates of the lateral cilia of the gill were measured by stroboscopic microscopy. Pre-treating gill preparations with PAS or EDTA blocked the neurotoxic effects of manganese, while ASA did not. In other experiments, animals exposed to three day treatments with manganese produced a dose dependent impairment of the dopaminergic, cilio-inhibitory system, which was decreased by co-treatment with PAS. The study shows that PAS protects the animal against neurotoxic effects of manganese and the mechanism of action of PAS in alleviating Manganism is more likely related to its chelating abilities than its anti-inflammatory actions.

The neurotoxic effects of manganese on the dopaminergic innervation of the gill of the bivalve mollusc, Crassostrea virginica.

We examined effects of manganese on the nervous system and innervation of lateral cilia of Crassostrea virginica. While essential in trace amounts, tissue manganese accumulation is neurotoxic, inducing Manganism, a Parkinson's-like disease in humans. Lateral cilia of the gill of C. virginica are controlled by a reciprocal serotonergic-dopaminergic innervation from their ganglia. Oysters were incubated 3 days in the presence of up to 1 mM manganese, followed by superfusion of the cerebral ganglia, visceral ganglia or gill with dopamine or serotonin. Beating rates of cilia were measured by stroboscopic microscopy of isolated gill preparations or gill preparations with the ipsilateral cerebral and/or visceral ganglia attached. Acute manganese treatments impaired the dopaminergic, cilio-inhibitory system, while having no effect on the serotonergic, cilio-excitatory system, which is in agreement with the proposed mechanism of manganese toxicity in humans. Manganese treatments also decreased endogenous dopamine levels in the cerebral and visceral ganglia, and gills, but not serotonin levels. We demonstrated that manganese disrupts the animal's dopaminergic system, and also that this preparation can be used to investigate mechanisms that underlie manganese neurotoxicity. It also may serve as a model in pharmacological studies of drugs to treat or prevent Manganism and other dopaminergic cell disorders.