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Microcystin congener– and concentration-dependent induction of Murine neuron apoptosis and Neurite degeneration

Microcystin congener– and concentration-dependent induction of Murine neuron apoptosis and Neurite degeneration

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FEURSTEIN, Daniel, Kerstin STEMMER, Julia KLEINTEICH, Tobias SPEICHER, Daniel DIETRICH, 2011. Microcystin congener– and concentration-dependent induction of Murine neuron apoptosis and Neurite degeneration. In: Toxicological Sciences. 124(2), pp. 424-431. ISSN 1096-6080. eISSN 1096-0929. Available under: doi: 10.1093/toxsci/kfr243

@article{Feurstein2011-12Micro-18624, title={Microcystin congener– and concentration-dependent induction of Murine neuron apoptosis and Neurite degeneration}, year={2011}, doi={10.1093/toxsci/kfr243}, number={2}, volume={124}, issn={1096-6080}, journal={Toxicological Sciences}, pages={424--431}, author={Feurstein, Daniel and Stemmer, Kerstin and Kleinteich, Julia and Speicher, Tobias and Dietrich, Daniel} }

Feurstein, Daniel Stemmer, Kerstin Cyanobacterial microcystins (MCs) represent a toxin group with > 100 variants, requiring active uptake into cells via organic anion–transporting polypeptides, in order to irreversibly inhibit serine/threonine-specific protein phosphatases. MCs are a human health hazard with repeated occurrences of severe poisonings. In the well-known human MC intoxication in Caruaru, Brazil (1996), patients developed signs of acute neurotoxicity, e.g., deafness, tinnitus, and intermittent blindness, as well as subsequent hepatotoxicity. The latter data, in conjunction with some animal studies, suggest that MCs are potent neurotoxins. However, there is little data to date demonstrating MC neuron-specific toxicity. MC exposure–induced cytotoxicity, caspase activity, chromatin condensation, and microtubule-associated Tau protein hyperphosphorylation (epitopes serine199/202 and serine396) were determined. Neurite degeneration was analyzed with confocal microscopy and neurite length determined using image analysis. MC-induced apoptosis was significantly increased by MC-LF and MC-LW, however, only at high concentrations (≥ 3MyM), whereas significant neurite degeneration was already observed at 0.5MyM MC-LF. Moreover, sustained hyperphosphorylation of Tau was observed with all MC congeners. The concentration- and congener-dependent mechanisms observed suggest that low concentrations of MC-LF and MC-LW can induce subtle neurodegenerative effects, reminiscent of Alzheimer’s disease type human tauopathies, and thus should be taken more seriously with regard to potential human health effects than the apical cytotoxicity (apoptosis or necrosis) demonstrated at high MC concentrations. Speicher, Tobias Kleinteich, Julia deposit-license 2011-12 Dietrich, Daniel Stemmer, Kerstin Dietrich, Daniel Microcystin congener– and concentration-dependent induction of Murine neuron apoptosis and Neurite degeneration Feurstein, Daniel Kleinteich, Julia Speicher, Tobias First publ. in: Toxicological Sciences ; 124 (2011), 2. - S. 424-431 2012-03-16T10:50:23Z eng 2012-12-14T23:25:03Z

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