p‐Aminosalicylic Acid (PAS) Reverses Neurotoxic Effects of Manganese on Dopamine Post‐Synaptic Receptors
TL;DRAbstract
Manganese (Mn) a neurotoxin causing Manganism disrupts dopamine (DA) neurotransmission. The neurotoxic mechanism of action is not fully resolved. Effective clinical treatments are lacking. Reports postulate Mn toxicity is more related to dysfunction of DA D2 receptors (D2DR) than degeneration of neurons. Cilia of gill lateral cells of Crassostrea virginica are innervated by cilio-inhibitory DA nerves. Mn treatment blocks effects of DA and post-synaptic DA receptors in lateral cells are D2 type. Applying p-aminosalicylic acid (PAS) with Mn prevented the toxic effect. We hypothesize PAS could reverse Mn neurotoxicity when applied after Mn. To test this we treated C. virginia up to 3 days with Mn (500 µM) followed by 5 more days with PAS (500 µM). Gills were excised, fixed, exposed to 1̊ antibodies against D2DR and FITC-linked 2̊antibodies, paraffin embedded, sectioned at 10 µm, then visualized on a fluorescence microscope. Fluorescence intensity was quantified using ImageJ software from
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Manganese (Mn) a neurotoxin causing Manganism disrupts dopamine (DA) neurotransmission. The neurotoxic mechanism of action is not fully resolved. Effective clinical treatments are lacking. Reports postulate Mn toxicity is more related to dysfunction of DA D2 receptors (D2DR) than degeneration of neurons. Cilia of gill lateral cells of Crassostrea virginica are innervated by cilio-inhibitory DA nerves. Mn treatment blocks effects of DA and post-synaptic DA receptors in lateral cells are D2 type. Applying p-aminosalicylic acid (PAS) with Mn prevented the toxic effect. We hypothesize PAS could reverse Mn neurotoxicity when applied after Mn. To test this we treated C. virginia up to 3 days with Mn (500 µM) followed by 5 more days with PAS (500 µM). Gills were excised, fixed, exposed to 1̊ antibodies against D2DR and FITC-linked 2̊antibodies, paraffin embedded, sectioned at 10 µm, then visualized on a fluorescence microscope. Fluorescence intensity was quantified using ImageJ software from
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