Moore Caroline E, Lein Pamela J, Puschner Birgit
Department of Molecular Biosciences, School of Veterinary Medicine, 1089 Veterinary Medicine Drive, 2225 VM3B, University of California, Davis, Davis, CA 95616, USA.
Toxins (Basel). 2014 Jun 10;6(6):1813-36. doi: 10.3390/toxins6061813.
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.
有害藻华通过受污染的饮用水使人类和动物接触微囊藻毒素（MCs）。虽然急性接触MCs后的肝毒性已有充分记录，但亚致死接触后的神经毒性却知之甚少。我们开发了一种新的统计方法，使用广义线性模型和拟二项分布族来分析成年秀丽隐杆线虫暴露于MC-LR或MC-LF 24小时后的神经毒性作用。使用趋化性试验确定毒素暴露对AWA与AWC感觉神经元功能的选择性影响。MCs呈现非单调反应，改变了AWA但未改变AWC功能，且MC-LF比MC-LR更具效力。为探究蛋白磷酸酶（PPs）在MC神经毒性中的潜在作用，我们评估了暴露于PP1抑制剂 tautomycin或PP2A抑制剂冈田酸24小时的线虫的趋化反应。冈田酸损害了AWA和AWC功能，而在所测试的浓度下，tautomycin对两种神经元细胞类型的功能均无影响。这些发现表明，MCs在不通过抑制PPs的机制导致AWC毒性的浓度下改变了AWA神经元。
