The pathophysiology of neurological risk from environmental toxins: Microcystin-LR leads to a decrease in neuron...

The presence of microcystin-LR (MC-LR) poses a grave threat to both ecosystems and public health. Some studies have indicated that MC-LR can result in neurotoxicity, yet the specific mechanisms and effects remain unclear. This research used brain organoid models and mouse models to investigate the neurotoxic effects and mechanisms associated with MC-LR exposure. Findings from microelectrode array (MEA) assessments demonstrated a statistically significant reduction in both discharge activity and the number of neurons in the cerebral organoid upon acute exposure to MC-LR (P < 0.05). TUNEL (TdT-mediated dUTP nick end labeling) staining indicated that MC-LR exposure led to neuronal death and reduced neuron numbers in brain organoids. Meanwhile, the exposure of 12-month-old mice to low concentrations of MC-LR (0, 1, 60, and 120 μg/L) was found to lead to a decrease in the number of neurons based on histopathological and biochemical analyses. Moreover, long-term exposure to MC-LR also activated the JNK/NF-κB signaling pathway in the hippocampal region of the mouse brain tissue. The qPCR analysis demonstrated increased expression levels of the inflammatory markers nlrp3, caspase-1, il-18, il-6, and the pyroptosis-related marker gsdmd in hippocampal neuron tissue from groups exposed to 60 μg/L and 120 μg/L of MC-LR in mice. These results are consistent with those of the Western blot analysis. This study elucidated that prolonged exposure to MC-LR triggered activation of the JNK/NF-κB signaling pathway, neuroinflammation, neuronal pyroptosis.