title: Extended Low-Dose Exposure to Saxitoxin Inhibits Neurite Outgrowth in Model Neuronal Cells.
abstract: The potent neurotoxin saxitoxin (STX) belongs to a group of structurally related analogues produced by both marine and freshwater phytoplankton. The toxins act by blocking voltage-gated sodium channels stopping the inflow of sodium ions and the generation of action potentials. Exposure from marine sources occurs as a result of consuming shellfish which have concentrated the toxins, and freshwater exposure can occur from drinking water although there have been no acute poisonings from the latter source to date. Previously, the majority of research into this group of toxins, collectively known as the paralytic shellfish toxins, has focused on acute exposure resulting in paralytic shellfish poisoning. While acute exposure guidelines exist for both sources, there are no chronic exposure guidelines and there has been minimal research into this pattern of exposure despite the known role of electrical activity in neurogenesis. We aimed to investigate this pattern of exposure and its potential effects on neurodevelopment using model neuronal cells. PC12 and SH-SY5Y cells were exposed to STX (0.25-3 μg/l) for 7 days, after which time they were stained with TRITC-Phalloidin, to observe adverse morphological effects. Cells exposed to STX had a significant decrease (18-85%) in long axonlike projections, instead exhibiting a significant increase in shorter projections classified as filopodia (p < 0.05). The results suggest that extended low-dose exposure to STX can inhibit proper neurite outgrowth at concentrations well below guideline levels for both sources of exposure making it a potential public health concern.
authors.affiliation: Discipline of Pharmacology, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Katie
authors.initials: K
authors.lastname: O'Neill
authors.affiliation: Discipline of Pharmacology, School of Medicine, The University of Adelaide, Adelaide, SA, Australia.
authors.forename: Ian F
authors.initials: IF
authors.lastname: Musgrave
authors.affiliation: Australian Water Quality Centre, South Australian Water Corporation, Adelaide, SA, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Humpage
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D016716:PC12 Cells; D051381:Rats; D012530:Saxitoxin / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D012530:Saxitoxin