Neurotoxicity of Microcystis exudates based on fish embryonic, human cellular and computational toxicology.

Cyanobacterial harmful algal blooms (cHABs), commonly dominated with Microcystis aeruginosa, threaten aquatic health by releasing toxic compounds. Neurotoxicity is one of the most concerning hazards of cHABs. In addition to the well-known neurotoxins such as anatoxin-a and saxitoxin, M. aeruginosa also release exudates (MaE) of complex chemical mixtures that cause neuro-impairment. Using a systematic toxicology test, including fish embryonic/ larval, human cellular and computational models, we tested the hypothesis that MaE mixtures damage the nervous health in animals. We found that MaE inhibited fish neurobehavior (such as touch response and swimming distance) which resulted from excitatory neurotransmitters (acetylcholine and dopamine) decreases. MaE also decreased the viability and proliferation of a human astrocyte cell line via damage to DNA and cytoskeleton. 46 of 72 neurotoxicity targets from the EPA's Toxicity Forecaster (ToxCast) database were affected by this MaE mixture. Neurotoxicity could be initiated via blocking calcium voltage-gated channel, antagonizing neurotransmitter receptors, or inhibiting solute carrier transporters, to impaire neurotransmission. We identified 9 neurotoxic MaE compounds with high affinity to those targets, including LysoPC(16:0), 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, egonol glucoside, and phytosphingosine. Our study enhances understanding of cHAB exudates' neurotoxicity, which may contribute to future water management. [ABSTRACT FROM AUTHOR]