Cytotoxicity Modulated by Cyanotoxins in Neuroblastoma SH-SY5Y Cells

Aquatic prokaryotic cyanobacteria (algal blooms) produce cyanotoxins (CTs), significant pollutants in aquatic ecosystems. Direct exposure to high-concentration CTs through inhalation, skin contact, or ingestion of contaminated water can lead to hepatotoxicity and neurotoxicity. However, the effect of exposure to CTs at low concentrations remains unclear. Given that CTs can cross the blood-brain barrier via organic anion transporting polypeptides (OATPs), we investigated the effect of acute exposure to low concentrations (10 nM and 50 nM) of CTs, namely microcystin-LR (MC-LR), nodularin (NOD), cylindrospermopsin (CYN), and known neurotoxin β-N-methylamino-l-alanine (BMAA) in neuroblastoma SH-SY5Y cells. Using MTT assays, we found that all tested CTs increased cell survival at low concentrations. MC-LR, NOD, and CYN regulated the expression of metabolic <i>CYP1A1</i>, <i>CYP1A2</i>, <i>CYP2D6</i>, <i>CYP2E1</i>, <i>CYP3A4</i>, and <i>VEGFA</i> expression differentially, whereas BMAA downregulates metabolic gene expression. CT exposure downregulates mitochondrial oxygen consumption rate in neuroblastoma SH-SY5Y cells, increases <i>IL-6</i>, <i>SOD1</i>, and <i>TNFα</i> expression, and enhances cell apoptosis. CTs also downregulated unfolded protein response-associated gene expression and increased Tau phosphorylation. Collectively, these findings suggest that acute exposure to low concentrations of CTs modulates neuroblastoma cell metabolism, Inflammatory signaling, and AD-related markers, highlighting a potential link between environmental toxin exposure and neurotoxicity.