saxitoxin and Cognition-Disorders

Toxins formed by organic micro-organisms may accumulate within certain tissues of predacious sea animals, which may serve as a source of seafood poisoning for the higher food chain. Such toxins are distinct from inorganic chemicals or infectious agents which may have contaminated the seafoods. Distinct clinical syndromes have emerged, and the individual toxins have been identified. Clinical manifestations of each begin with a gastrointestinal prodrome and headache, followed by sensorimotor deficits. Bulbar and cognitive changes are associated with the more lethal tetrodotoxin, saxitoxin, and domoic acid toxin. Tetrodotoxin and saxitoxin block sodium channels, while ciguatoxin opens them. Domoic acid stimulates excitatory amino acids at the NMDA receptors.

Topics: Brain Diseases; Bulbar Palsy, Progressive; Ciguatoxins; Cognition Disorders; Foodborne Diseases; Gastrointestinal Diseases; Headache; Humans; Mannitol; Psychomotor Disorders; Receptors, N-Methyl-D-Aspartate; Saxitoxin; Seafood; Sodium Channels; Tetrodotoxin

Saxitoxin (STX), as a type of paralytic shellfish poisoning (PSP), is gaining widespread attention due to its long existence in edible shellfish. However, the mechanism underlying STX chronic exposure-induced effect is not well understood. Here, we evaluated the neurotoxicity effects of long-term low-dose STX exposure on C57/BL mice by behavioral tests, pathology analysis, and hippocampal proteomics analysis. Several behavioral tests showed that mice were in a cognitive deficiency after treated with 0, 0.5, 1.5, or 4.5 μg STX equivalents/kg body weight in the drinking water for 3 months. Compared with control mice, STX-exposed mice exhibited brain neuronal damage characterized by decreasing neuronal cells and thinner pyramidal cell layers in the hippocampal CA1 region. A total of 29 proteins were significantly altered in different STX dose groups. Bioinformatics analysis showed that protein phosphatase 1 (Ppp1c) and arylsulfatase A (Arsa) were involved in the hippo signaling pathway and sphingolipid metabolism pathway. The decreased expression of Arsa indicates that long-term low doses of STX exposure can cause neuronal inhibition, which is a process related to spatial memory impairment. Taken together, our study provides a new understanding of the molecular mechanisms of STX neurotoxicity.

Topics: Animals; Behavior, Animal; CA1 Region, Hippocampal; Cognition Disorders; Dose-Response Relationship, Drug; Hippocampus; Memory Disorders; Mice; Mice, Inbred C57BL; Neurons; Neurotoxicity Syndromes; Proteomics; Pyramidal Cells; Saxitoxin