Acrylamide induces neurotoxicity in zebrafish (Danio rerio) via NLRP3-mediated pyroptosis

Acrylamide (ACR) is widely used in water treatment, cosmetics, dyes, paper manufacturing, and other industries. Evidence suggests that ACR exposure causes selective neurotoxicity in humans. The primary symptoms include extremity numbness, skeletal muscle weakness, and ataxia, skeletal muscle weakness. An experimental zebrafish (Danio rerio) embryo model was used in this study to assess the impact of ACR toxicity on the development of the zebrafish nervous system. The results showed that neurodevelopmental disorders, inflammatory reactions, and oxidative stress were common in zebrafish exposed to ACR. Furthermore, ACR exposure induces pyroptotic phenotypical nerve cells, pyroptosis-related protein activation, and inflammasome NLR family pyrin domain-containing 3 (NLRP3) expression. Caspy and Caspy2 expression was knocked down via CRISPR/Cas9 to further investigate the pyroptotic mechanism, showing that these two targets alleviated the inflammatory reaction and neurodevelopmental disorder caused by ACR. Moreover, the Caspy-mediated classic pathway may be vital for the pyroptosis caused by ACR. In conclusion, this study is the first to show that ACR can activate NLRP3 inflammation to cause neurotoxicity in zebrafish via the Caspy pathways, which differs from the traditional exogenous infection model.