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 ri vers, are believed to secrete toxins that kill fish and produce short-term memory loss in humans. Only one or two of Pfiesferia's multiple stages secr ete the toxin, and only under certain environmental conditions. Thus, neith er the presence of Pfiesteria nor fish kill alone can be indicative of toxi n presence. The objective of this study was to identify the mammalian molec ular brain target for the toxin that is associated with decrements in memor y. Seven rat brain neurotransmitter receptors were selected to study becaus e of their reported roles in cognitive function: receptors for nicotine, mu scarine, AMPA/kainate, N-methyl-D-aspartate (NMDA), gamma -aminobutyric aci d, and dopamine 1 and 2. The effects of 17 environmental and laboratory sam ples on radioactive ligand binding to these receptors were studied. Of the seven receptors, binding only to the NMDA receptor was inhibited by only th e two Pfiesteria-containing waters (identified by PCR) that also killed fis h, and not by any of the other 15 samples tested. It is suggested that inhi bition of NMDA-receptor binding is the cause of memory loss in exposed huma ns. Thus, it could be a useful biomarker for the toxin's presence in rivers for decisions on closures and for identification of the fractions containi ng the toxin during its purification. Knowledge of the toxin's molecular ta rget, and how it affects its function, also leads to suggestions for therap eutics to use in animal models. (C) 2000 Academic Press.