In humans, manganese is an environmental neurotoxin that when chronically inhaled can cause Manganism, a Parkinson’s-like disease. The mechanism by which manganese produces this dysfunction is not fully resolved . Manganism involves disruption of dopamine neurotransmission, but it is different from Parkinson’s disease . Current treatments for Parkinson’s do not resolve the symptoms of Manganism . Previously, our lab determined that the bivalve Crassostrea virginica, when exposed to high levels of manganese, accumulated the metal in its tissues and demonstrated a dysfunction on the cilio-inhibitory dopaminergic innervation of the gill. Gill lateral cell cilia of C. virginica are innervated by serotonin and dopamine nerves from their ganglia. Dopamine is cilio -inhibitory, while serotonin is cilio-excitatory. Our lab has shown that acute and short-term manganese treatments selectively blocks the cilio-inhibitory effect of dopamine , but not the cilio-excitatory effect of serotonin. Our lab also showed that the drugs p-aminosalicylic acid and taurine reduced the tissue levels if manganese and alleviated the neurotoxic action of manganese on the dopaminegic system. Recently, reports suggest the drug rasagiline , a monoamine oxidase inhibitor (MAO-I) could protect against manganese induced reactive oxygen species , and offer a benefit to p atients with Manganism. In this study we hypothesized rasagiline would reduce the neurotoxic actions of manganese on the cilio -inhibitory effects of dopamine in C. virginica gill. To test this, we conducted dopamine dose responses on excised gills of animals treated with manganese (10-4 M) for 5 days. Gill lateral cell cilia activity was measured by stroboscopic microscopy. Cilia of control lateral gill cells that were first activated by serotonin (10-5M) responded normally to the dopamine (10-7 - 10-3 M) dose response with the appropriate decrease in cilia beating rates from about 20 beats/second to about 0. Manganese treated animals showed a statistically significant disruption of the dopamine cilio-inhibitory dose response. Applying rasagiline to the gills of the manganese treated animals did not significantly reduce the neurotoxic effect of manganese on the cilio -inhibitory actions of dopamine. This project shows that more studies need to be done with rasagiline to determine its possible effectiveness and therapeutic mechanism of action. Future experiments should be conducted with increased rasagiline doses and/or increase duration of drug exposure . The bivalve mollusc gill is a useful model to study regulatory mechanisms of ciliary activity as well as the pharmacology of drugs affecting biogenic amines in nervous systems. The information from this present study should be of interest to those studying the mechanism of action of manganese toxicity and others designing drug to alleviate the symptoms of Manganism.
This work was supported in part by grants 0537231071 of the CSTEP Program of NYSED, P120A210054 of the MSEIP Program of the DoEd, NIH grant K12GM093854-07A1 IRACDA Program of Rutgers University, and CCUNY I-CORPS of NSF.