Meeting Abstract
Manganese (Mn) is a neurotoxin causing Manganism, a Parkinsons-like disease in humans. Mn neurotoxicity involves disruption of dopaminergic neurotransmission. The roxic mechanism is not fully resolved and is thought to be more related to downstream neuronal pathways than deficits in nigrostriatal function. Lack of effective treatment for Mn toxicity is a major obstacle. Recently, p-Aminosalicylic acid (PAS) was reported an effective treatment; however its mechanism of action is unclear. Gill lateral cell cilia of Crassostrea virginica are controlled by serotonergic-dopaminergic innervations from their ganglia. Dopamine (DA) causes cilio-inhibition, serotonin cilio-excitation. Our lab showed Mn blocks cilio-inhibitory effects of DA and this is prevented by co-treatments with PAS. We hypothesize PAS would reverse the neurotoxic actions of Mn when applied after Mn. We treated C. virginia for 3 days with Mn (500 mM) followed by 5 days with PAS (500 mM). Ciliary activity of gill lateral cells was measured by stroboscopic microscopy. We found, in congruence with our earlier studies, Mn treatments disrupts DA (10-6 – 10-4 M) induced cilio-inhibitory of gill lateral cells. In addition we show PAS treatments after Mn exposure reversed this and cilia of lateral gill cells responded normally to DA with appropriate decreases in beating rates. The study shows PAS effectively reverses neurotoxic effects of Mn on the physiological response of a dopaminergic system innervating gill lateral ciliated cells. These finding are helpful to furthering understanding of the mechanism underlying Mn neurotoxicity and in the search for effective treatments for Manganism, and in particular concerning PAS as a therapeutic agent.
