The N-methyl-D-aspartate neurotransmitter receptor is a mammalian brain target for the dinoflagellate Pfiesteria piscicida toxin.
Blooms of Pfiesteria piscicida, a dinoflagellate in eastern U.S. coastal rivers, are believed to secrete toxins that kill fish and produce short-term memory loss in humans. Only one or two of Pfiesteria's multiple stages secrete the toxin, and only under certain environmental conditions. Thus, neither the presence of Pfiesteria nor fish kill alone can be indicative of toxin presence. The objective of this study was to identify the mammalian molecular brain target for the toxin that is associated with decrements in memory. Seven rat brain neurotransmitter receptors were selected to study because of their reported roles in cognitive function: receptors for nicotine, muscarine, AMPA/kainate, N-methyl-D-aspartate (NMDA), gamma-aminobutyric acid, and dopamine 1 and 2. The effects of 17 environmental and laboratory samples on radioactive ligand binding to these receptors were studied. Of the seven receptors, binding only to the NMDA receptor was inhibited by only the two Pfiesteria-containing waters (identified by PCR) that also killed fish, and not by any of the other 15 samples tested. It is suggested that inhibition of NMDA-receptor binding is the cause of memory loss in exposed humans. Thus, it could be a useful biomarker for the toxin's presence in rivers for decisions on closures and for identification of the fractions containing the toxin during its purification. Knowledge of the toxin's molecular target, and how it affects its function, also leads to suggestions for therapeutics to use in animal models.
El-Nabawi
A
A
Department of Pharmacology and Experimental Therapeutics, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Quesenberry
M
M
Saito
K
K
Silbergeld
E
E
Vasta
G
G
Eldefrawi
A
A
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002458:Cell Fractionation; D004784:Environmental Monitoring / Q000379:methods; D008024:Ligands; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D020045:Pfiesteria piscicida; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013045:Species Specificity; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D008024:Ligands; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D014874:Water Pollutants, Chemical