Nanoplastics exacerbate lead exposure-induced developmental neurotoxicity by disrupting gut integrity in Drosophila

Lead (Pb), a neurotoxic heavy metal, can accumulate in the central nervous system (CNS) by crossing the blood-brain barrier and cause damage, while micro-nanoplastics (MNPs) are known to absorb Pb and enhance its toxicity. However, the synergistic effects of co-exposure on neurodevelopment remain unclear. This study established a Drosophila model to systematically evaluate the neurodevelopmental toxicity of combined nanoplastics (NPs) and Pb exposure. Behavioral tests revealed that co-exposure significantly exacerbated learning and memory deficits compared to Pb exposure alone, accompanied by reduced pupation and eclosion rates, as well as delayed development. Female flies showed decreased survival rates and more severe impairments in climbing and motor activity. Mechanistic investigations indicated that co-exposure promoted Pb accumulation in neural tissues, aggravated oxidative stress (elevated SOD activity, decreased CAT activity, and increased MDA levels), disrupted neuromuscular junction (NMJ) development and Mushroom body (MB) axon guidance, and induced intestinal damage (increased epithelial cell mortality and microvilli structural abnormalities). This study demonstrates that NPs synergistically enhance Pb-induced neurodevelopmental toxicity through multiple pathways, providing critical toxicological evidence for the health risks of environmental composite pollutants.