The overall objective of this project is to identify the neurotoxic agent(s) produced by the dinoflagellate Pfiesteria piscicidae, and to understand the mechanisms by which a range of neuropsychological deficits, particularly cognitive deficits are induced in exposed persons. The project will benefit other parts of this Program Project, and will make contributions to understanding how and under what conditions the toxin produced by Pfiesteria-like dinoflagellates in Maryland (PTX) affects neurobiologic function in humans. It's specific goals are (1) to screen for neuroactive agent(s) produced by Pfiesteria-like dinoflagellates by utilizing in vitro assays of cellular metabolism, neurotransmitter receptor and transporter binding, and simple assays of neuronal function; (2) to determine how conditions of dose, duration, and route(s) of exposure affect response by testing effects of the isolated PTX(s) on behavior and neurochemistry in in vivo models of learning, and (3) to understand the molecular mechanism(s) of PTX neurotoxicity using the most up to date neurochemical and electrophysiological techniques (patch clamp and confocal microscopy) and receptor transporter radio-ligand binding and functional assays, as well as the effect of PTX on cell metabolism using the Cytocensor microphysiometer. Knowledge of the mechanism(s) of action of PTX will lead to suggestions for therapeutics.
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