Taurine Protects Against the Neurotoxic Effects of Manganese on the Dopaminergic Control of Lateral Cell Membrane Potential and Ciliary Response in Gill of Crassostrea virginica

Manganese is a neurotoxin causing manganism, a Parkinson's‐like disease involving disruption of dopaminergic neurotransmission. The mechanism by which manganese produces this dysfunction is not fully resolved. Unlike Parkinson's disease, reports postulate that manganese neurotoxicity is more likely related to downstream neuronal pathways rather than deficits in nigrostriatal function. Lack of effective treatment for manganism has been a major obstacle in its clinical management. The cilia of lateral cell in gill of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. Dopamine (DA) hyperpolarizes the cell and causes cilio‐inhibition, while serotonin depolarizes and causes cilio‐excitation. Previous work of our lab showed acute and short‐term manganese treatments blocked the cilio‐inhibitory effect of DA. This neurotoxic action of manganese could be prevented by the drug p‐aminosalicylic acid or by taurine, an amino acid with efficacy in other neurodegenerative disorders. In this study we hypothesize that taurine would effectively prevent the toxic actions of manganese on both dopaminergic membrane hyperpolarization and lateral cilia inhibition. To test this we conducted acute experiments on DA dose responses (10 −6 – 10 −3 M) of manganese treated excised gill in the presence or absence of taurine. Ciliary activity of gill lateral cells was measured by stroboscopic microscopy and expressed as beats/min ± sem. Cell membrane potentials were simultaneously measured using the fluorescent dye DiBAC 4 (3). In control gill, the lateral cells responded normally to the DA dose response showing the appropriate decrease in cilia beating rates and membrane hyperpolarization. Gills treated with manganese (2 × 10 −4 M) had a disrupted DA response, cilio‐inhibition was impaired and the membrane did not hyperpolarize. Taurine treatment (2 × 10 −4 M) effectively prevented these neurotoxic effects in manganese treated gill. This physiological study in C. virginica shows that manganese disrupts the dopaminergic post‐synaptic response of lateral cells preventing membrane hyperpolarization as well disrupting cilio‐inhibition, and that taurine effectively blocked these neurotoxic actions. These findings are helpful in furthering the understanding of the mechanism of manganese neurotoxicity and provides evidence suggesting taurine be further investigated as a potential therapeutic agent for manganism. Support or Funding Information This work was supported in part by grant 2R25GM06003 of the Bridge Program of NIGMS, NIH grant K12GM093854‐07A1 IRACDA Program of Rutgers University and 604060048 of PSC‐CUNY. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .