Novel insights into cyanobacterial (microcystins) neurotoxicity in rats: hepatic encephalopathy

Microcystis, a commonly occurring genus of bloom-forming cyanobacteria, can produce numerous secondary metabolites, including microcystins (MCs), which are hepatotoxic and neurotoxic to humans and animals. However, the mechanisms of cyanobacterial neurotoxicity associated with MCs have not yet been clarified. This study reports the first observations of hepatic encephalopathy (HE) after exposure to Microcystis bloom extracts (MEs), which contained MCs. Mechanisms of toxicity were studied in rats exposed to MEs by use of a single intraperitoneal injection of 80 μg MC-LR equivalents/kg, body mass. Abnormal serum biochemical markers of hepatic functions and histopathological damage of liver and cerebral cortex were observed. Specifically, Alzheimer type II astrocytes, histological markers of HE, were observed. Motor impairment and significantly increased concentrations of ammonia in serum, increased activities of glutamine synthetase, and concentrations of glutamine in the cerebral cortex were detected, which indicated occurrence of HE. Mechanisms of HE, including ammonia poisoning, oxidative stress and inflammation, were confirmed by real-time quantitative PCR and transcriptomics. Also, transcriptomics revealed that zinc ions dyshomeostasis and ferroptosis are involved in the development of HE. This study presents novel insights into neurotoxic symptoms in human poisonings caused by Microcystis, links neurotoxicity in the brain to the liver, i.e., the liver-brain axis, and provides a new perspective on the multi-organ toxicity of Microcystis and a basis for developing treatments.