Mechanisms by which Ganglioside GM1, a specific type of glycosphingolipid, ameliorates BMAA-induced neurotoxicity in early-life stage of zebrafish embryos.

The neurotoxin β-methylamino-L-alanine (BMAA) produced by cyanobacteria is widely present in foods and dietary supplements, posing a significant threat to human health. Ganglioside GM1 (GM1) has demonstrated potential for treating neurodegenerative diseases; however, its ability to prevent BMAA-induced neurotoxicity remains uncertain. In this study, zebrafish embryos were treated with Ganglioside GM1 to investigate its neuroprotective effects against BMAA exposure and the underlying mechanisms. Exposure to BMAA (400 μM) resulted in increased malformation rate and heart rates in zebrafish embryos at 72 h post-fertilization, along with the decreased survival rates. Conversely, GM1 intervention rescued BMAA-induced movement disorders and brain cell apoptosis, and oxidative stress was alleviated. In addition, GM1 inhibited the neurotoxic effects of BMAA in zebrafish embryos, as indicated by the up-regulation of genes related to neuron development (gpx1a, bdnf, ngfb, and islet-1) and the down-regulations of neurodegeneration-related genes (cdk5, gfap, and nptxr). GM1 treatment restored 261 differentially expressed genes (DEGs) identified through RNA sequencing, with the most enriched DEGs related to the mitogen-activated protein kinase (MAPK) signaling pathway (P < 0.05, 47 genes). GM1 modulated MAPK-targeted gene expression at the mRNA level. These findings suggest that GM1 alleviates BMAA-induced neurotoxicity in the early-life stage of zebrafish embryos. The neuroprotective mechanism may involve the MAPK pathway, offering new insights into lipid signaling for the prevention of neurotoxic hazards to biological health.