Blood-brain barrier disruption and inflammation reaction in mice after chronic exposure to Microcystin-LR

Microcystin-leucine-arginine (MC-LR), which produced by toxic cyanobacteria and widely present in eutrophic waters, has been shown to have potent acute hepatotoxicity. MC-LR has been revealed to inflict damage to brain, while the neurotoxicity of chronic exposure to MC-LR and mechanisms underlying it are still confusing. Here, the mice were exposed to MC-LR dissolved in drinking water at dose of 1, 7.5, 15, and 30 μg/L for consecutive 180 days. MC-LR accumulated in mouse brains and impaired the blood-brain barrier by inducing the expression of matrix metalloproteinase-8 (MMP-8), which was regulated by NF-κB, c-Fos and c-Jun. Furthermore, MC-LR exposure induced microglial and astrocyte activation and resultant neuroinflammatory response. This study highlights the risks to human health of the current microcystin exposure.