palytoxin and brevetoxin

Synapses are specialised structures where interneuronal communication takes place. Not only brain function is absolutely dependent on synaptic activity, but also most of our organs are intimately controlled by synaptic activity. Synapses re therefore an ideal target to act upon and poisonous species have evolved fascinating neurotoxins capable of shutting down neuronal communication by blocking or activating essential components of the synapse. By hijacking key proteins of the communication machinery, neurotoxins are therefore extremely valuable tools that have, in turn, greatly helped our understanding of synaptic biology. Moreover, analysis and understanding of the molecular strategy used by certain neurotoxins has allowed the design of entirely new classes of drugs acting on specific targets with high selectivity and efficacy. This chapter will discuss the different classes of marine neurotoxins, their effects on neurotransmitter release and how they act to incapacitate key steps in the process leading to synaptic vesicle fusion.

Topics: Acrylamides; Amino Acid Sequence; Animals; Calcium Channel Blockers; Calcium Channels; Ciguatoxins; Cnidarian Venoms; Ion Channels; Marine Toxins; Models, Molecular; Molecular Sequence Data; Neurotoxins; Neurotransmitter Agents; Oxocins; Potassium Channels; Saxitoxin; Sea Anemones; Synaptic Transmission; Tetrodotoxin

At the European level, detection of marine neurotoxins in seafood is still based on ethically debated and expensive in vivo rodent bioassays. The development of alternative methodologies for the detection of marine neurotoxins is therefore of utmost importance. We therefore investigated whether and to what extent a multielectrode array (MEA) approach can be used as an in vitro alternative for screening of marine neurotoxins potentially present in seafood.. This MEA approach utilizes rat cortical neurons comprising a wide range of ion channels/pumps and neurotransmitter receptors targeted by marine neurotoxins. We tested the effects of neurotoxic model compounds, pure marine neurotoxins, and extracts from contaminated seafood on neuronal activity of rat cortical neurons cultured on commercial 48-well plates to increase throughput.. We demonstrate that the MEA approach has a sensitivity of 88% (7/9 model compounds, 6/6 pure marine neurotoxins, and 2/2 marine neurotoxins present in seafood extracts were correctly identified) and a good reproducibility compared to existing in vitro alternatives. We therefore conclude that this MEA-based approach could be a valuable tool for future food safety testing.

Topics: Acrylamides; Animal Use Alternatives; Animals; Cells, Cultured; Ciguatoxins; Cnidarian Venoms; Fishes; Food Contamination; Food Safety; Kainic Acid; Marine Toxins; Neurons; Neurotoxins; Oxocins; Rats; Rats, Wistar; Reproducibility of Results; Seafood; Tetrodotoxin