Microcystins alter chemotactic behavior in Caenorhabditis elegans by selectively targeting the AWA sensory neuron

Toxins (Basel). 2014 Jun 10;6(6):1813-36. doi: 10.3390/toxins6061813.

Abstract

Harmful algal blooms expose humans and animals to microcystins (MCs) through contaminated drinking water. While hepatotoxicity following acute exposure to MCs is well documented, neurotoxicity after sub-lethal exposure is poorly understood. We developed a novel statistical approach using a generalized linear model and the quasibinomial family to analyze neurotoxic effects in adult Caenorhabditis elegans exposed to MC-LR or MC-LF for 24 h. Selective effects of toxin exposure on AWA versus AWC sensory neuron function were determined using a chemotaxis assay. With a non-monotonic response MCs altered AWA but not AWC function, and MC-LF was more potent than MC-LR. To probe a potential role for protein phosphatases (PPs) in MC neurotoxicity, we evaluated the chemotactic response in worms exposed to the PP1 inhibitor tautomycin or the PP2A inhibitor okadaic acid for 24 h. Okadaic acid impaired both AWA and AWC function, while tautomycin had no effect on function of either neuronal cell type at the concentrations tested. These findings suggest that MCs alter the AWA neuron at concentrations that do not cause AWC toxicity via mechanisms other than PP inhibition.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bacterial Toxins / pharmacology*
  • Behavior, Animal / drug effects
  • Caenorhabditis elegans / drug effects*
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / antagonists & inhibitors
  • Caenorhabditis elegans Proteins / metabolism
  • Chemoreceptor Cells / drug effects*
  • Chemoreceptor Cells / enzymology
  • Chemoreceptor Cells / metabolism
  • Chemotaxis / drug effects*
  • Enzyme Inhibitors / pharmacology
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Marine Toxins
  • Microcystins / pharmacology*
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Neurotoxins / pharmacology*
  • Olfactory Receptor Neurons / drug effects
  • Olfactory Receptor Neurons / enzymology
  • Olfactory Receptor Neurons / metabolism
  • Osmolar Concentration
  • Protein Phosphatase 1 / antagonists & inhibitors
  • Protein Phosphatase 1 / metabolism
  • Protein Phosphatase 2 / antagonists & inhibitors
  • Protein Phosphatase 2 / metabolism
  • Reproducibility of Results

Substances

  • Bacterial Toxins
  • Caenorhabditis elegans Proteins
  • Enzyme Inhibitors
  • Isoenzymes
  • Marine Toxins
  • Microcystins
  • Nerve Tissue Proteins
  • Neurotoxins
  • microcystin-LF
  • Protein Phosphatase 1
  • Protein Phosphatase 2
  • cyanoginosin LR