ToxSci Advance Access originally published online on May 12, 2004
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Toxicological Sciences 80, 74-82 (2004)
Toxicological Sciences vol. 80 no. 1 © Society of Toxicology 2004; all rights reserved.
The Marine Toxin Dinophysistoxin-2 Induces Differential Apoptotic Death of Rat Cerebellar Neurons and Astrocytes
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* Biochemistry and Molecular Biology Department, University of Oviedo, Oviedo, Spain; PROTEOBIO, Mass Spectrometry Center for Proteomics and Biotoxin Research, Department of Chemistry, Cork Institute of Technology, Bishopstown, Cork, Ireland; and Psychology Department, University of Oviedo, Oviedo, Spain
Received February 11, 2004; accepted March 26, 2004
Diarrhetic shellfish poisoning (DSP) toxins of algal origin are frequent contaminants of coastal waters and seafood. The potential risk for human health due to the continuous presence of these toxins in food has not been clearly established. We have used cerebellar primary cultures to investigate the effects of the DSP toxin dinophysistoxin-2 (DTX-2) on central nervous system neurons and glial cells. Exposure to DTX-2 produced neurotoxicity at concentrations starting at 2.5 nM, characterized first by disintegration of neurites and later by cell death. DTX-2-induced neurodegeneration required long exposures (at least 20 h), involved DNA fragmentation and condensation and fragmentation of chromatin, typical hallmarks of apoptosis, and required the synthesis of new proteins. The concentration that reduced by 50% the maximum neuronal survival after 24 h exposure to DTX-2 (EC5024) was 
8 nM. Morphology and viability of glial cells remained unaffected up to at least 15 nM DTX-2. Higher concentrations of the toxin caused strong shrinkage of glial cell bodies and retraction of processes, and a significant reduction of glial cell viability. Glial toxicity by DTX-2 involved typical apoptotic condensation and fragmentation of chromatin. Compared to neurons, the effect on glial cells was a much shorter process, and extensive glial degeneration and death occurred after 7 h exposure to DTX-2 (EC507 50 nM; EC5024 30 nM). Although further experiments are needed to confirm these toxic actions in vivo, our in vitro data suggest that chronic exposure to amounts of DSP toxins below the current safety regulatory limits may represent a risk for human health that should be taken into consideration.
Key Words: dinophysistoxins; diarrhetic shellfish poisoning; neurotoxicity; apoptosis; cerebellar neurons; glial cells.
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