TY - JOUR
T1 - The N-methyl-D-aspartate neurotransmitter receptor is a mammalian brain target for the dinoflagellate Pfiesteria piscicida toxin
AU - El-Nabawi, Ahmed
AU - Quesenberry, Michael
AU - Saito, Keiko
AU - Silbergeld, Ellen
AU - Vasta, Gerardo
AU - Eldefrawi, Amira
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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), γ-aminobutyric acid, and dopamine 1 and 2. The effects of 17 environmental and laboratory samples on radio-active 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. (C) 2000 Academic Press.
AB - 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), γ-aminobutyric acid, and dopamine 1 and 2. The effects of 17 environmental and laboratory samples on radio-active 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. (C) 2000 Academic Press.
KW - Brain neurotransmitter receptors
KW - Memory loss
KW - N-methyl-D-aspartate receptor
KW - Neurotoxicity
KW - Pfiesteria piscicida
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U2 - 10.1006/taap.2000.9042
DO - 10.1006/taap.2000.9042
M3 - Article
C2 - 11076700
AN - SCOPUS:0034669113
VL - 169
SP - 84
EP - 93
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 1
M1 - 99042
ER -