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The differential effects of microcystin-LR on mitochondrial DNA in the hippocampus and cerebral cortex

Wang, Xiaofen, Xu, Lizhi, Li, Xinxiu, Chen, Jingwen, Zhou, Wei, Sun, Jiapeng, Wang, Yaping
Environmental pollution 2018 v.240 pp. 68-76
Cyanobacteria, aquatic animals, cerebral cortex, chronic exposure, drinking water, genotoxicity, hippocampus, histopathology, humans, kidneys, liver, mice, microcystin-LR, mitochondrial DNA, neurons, neurotoxicity, oral administration
Microcystin-LR (MC-LR) is the most abundant toxicant among microcystin variants produced by cyanobacteria. MC-induced toxicity is broadly reported to pose a threat to aquatic animals and humans and has been associated with the dysfunction of some organs such as liver and kidney. However, MC-induced neurotoxicity has not been well characterized after long-term exposure. This study was designed to investigate the neurotoxic effects after chronic oral administration of MC-LR. In our trial, C57/BL6 mice received MC-LR at 0, 1, 5, 10, 20 and 40 μg/L in drinking water for twelve months. Our data demonstrated that mitochondrial DNA (mtDNA) damage was evident in the damaged neurons as a result of chronic exposure. Histopathological abnormalities and mtDNA damage were observed in the hippocampus and cerebral cortex. Furthermore, MC-LR exerted distinct effects on these two brain regions. The hippocampus was more susceptible to the treatment of MC-LR compared with the cerebral cortex. However, no strong relationships were observed between the genotoxic effects and exposure doses. In conclusion, this study has provided a mtDNA-related mechanism for underlying chronic neurotoxicity of MC-LR and suggested the presence of differential toxicant effects on the hippocampus and cerebral cortex.