title: The marine toxin dinophysistoxin-2 induces differential apoptotic death of rat cerebellar neurons and astrocytes.
abstract: 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 (EC50(24)) was approximately 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 (EC50(7) approximately 50 nM; EC50(24) approximately 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.
authors.affiliation: Biochemistry and Molecular Biology Department, University of Oviedo, Oviedo, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Pérez-Gómez
authors.forename: Armando
authors.initials: A
authors.lastname: García-Rodríguez
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: James
authors.forename: Amaia
authors.initials: A
authors.lastname: Ferrero-Gutierrez
authors.forename: Antonello
authors.initials: A
authors.lastname: Novelli
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Fernández-Sánchez
mesh_terms: D000818:Animals; D017209:Apoptosis; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D049872:Bivalvia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D008387:Marine Toxins / Q000633:toxicity*; D016501:Neurites / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D020258:Neurotoxicity Syndromes / Q000473:pathology; D019319:Okadaic Acid / Q000031:analogs & derivatives; D018384:Oxidative Stress / Q000187:drug effects; D011714:Pyrans / Q000633:toxicity*; D051381:Rats
chemical_list: D008387:Marine Toxins; D011714:Pyrans; D019319:Okadaic Acid; C076221:dinophysistoxin 2