Penconazole induces developmental neurotoxicity by activating autophagy and neuronal apoptosis in zebrafish.

Penconazole (PEN), a systemic triazole fungicide, is widely used in agriculture. Despite frequent detection in ecosystems, its neurotoxic potential remains poorly understood. This study investigated PEN-induced developmental neurotoxicity and underlying mechanisms in zebrafish embryos. The results showed that PEN exposure impaired survival and development, disrupted locomotor and social behaviors, inhibited central nervous system (CNS) neurogenesis and motor neuron axon growth in HuC:egfp and hb9:egfp transgenic zebrafish, reduced cholinesterase activities and the number of Nissl bodies in the brain, and downregulated neurodevelopmental gene expression. In addition, PEN activated autophagy, subsequently triggering neuronal apoptosis in the zebrafish brain. These neurotoxic effects were effectively reversed by 3-methyladenine (3-MA, an autophagy inhibitor), suggesting the involvement of autophagy activation in PEN-induced neurotoxicity. Overall, our findings confirm PEN's neurotoxicity and implicate autophagy-mediated neuronal apoptosis as a key mechanism.