Taurine Prevents the Neurotoxic Effects of Manganese on the Physiological Response of a Cilio‐Inhibitory Dopaminergic System
Authors: Fatoke‐Osobukola Ernest , Ernest Krystle , Carroll Margaret A , Catapane Edward J 
Published: November 2023

Manganese is a neurotoxin causing Manganism, a Parkinson's‐like disease that involves disruption of dopaminergic neurotransmission. The mechanism by which manganese produces this dysfunction is not fully resolved and unlike Parkinson's disease, reports postulate the underlying mechanism of manganese neurotoxicity is more likely related to downstream neuronal pathways than deficits in nigrostriatal function. Lack of effective treatment for Manganism has been a major obstacle in its clinical management. Gill lateral cell cilia of Crassostrea virginica are controlled by serotonergic‐dopaminergic innervations from their ganglia. Dopamine is the neurotransmitter causing cilio‐inhibition and serotonin causes cilio‐excitation. Previous work of our lab showed acute and short‐term manganese treatments block the cilio‐inhibitory effect of dopamine and that the neurotoxic action of manganese could be reversed by the drug p‐Aminosalicylic acid (PAS). Recently, reports suggest the amino acid taurine may be worth investigating as a neuroprotective agent for Manganism because of its efficacy in other neurodegenerative diseases. We hypothesize taurine would reverse the neurotoxic actions of manganese on the cilio‐inhibitory effects of dopamine in C. virginica gill. To test this we conducted acute tissue experiments testing dopamine dose responses (10−6–10−3 M) on excised gill treated with manganese (10−3 M) for 10 minutes in the presence or absence of taurine (10−8–10−4 M). Ciliary activity of gill lateral cells was measured by stroboscopic microscopy and expressed as beats/min ± sem. Cilia of control gill lateral cells showed the normal cilio‐inhibitory effect to the dopamine dose response, and as previously reported, the cilio‐inhibitory effect due to dopamine dose responses was blocked when gill lateral cells were treated with manganese. However taurine treatments (10−8–10−4 M), after manganese exposure, effectively prevented the neurotoxic effects of manganese and the tissue regained the appropriate cilio‐inhibitory dose‐response to dopamine. The decrease in manganese neurotoxicity due to taurine was determined to have an ED50 of about 10−6 M. We also conducted short‐term experiments in which whole animal C. virginica were treated for 3 or 6 days with manganese (500 μM) with or without taurine (500 μM). Control animals were sham treated. The effect of treating whole animals with manganese on disrupting the cilio‐inhibitory dose response of dopamine (10−6–10−4 M) in gill lateral cells was again prevent by taurine. This study shows taurine is effective in preventing manganese neurotoxicity on the physiological response of a cilio‐inhibitory dopaminergic system in C. virginica. These findings are helpful in furthering the understanding of the mechanism of manganese neurotoxicity and provides evidence suggesting taurine should be further investigated as a potential therapeutic agent for Manganism.

Support or Funding Information

This work was supported by 2R25GM06003 of the Bridge Program of NIGMS and a Carnegie Foundation award.