Karmakar_2026_Neurosci_611_377

The use of copper oxide nanoparticles (CuO NPs) is increasing in biomedical applications and various industrial sectors. The increased use of these nanoparticles raises concerns regarding their potential neurotoxicological consequences on copper homeostasis. The present study established a CuO NP feeding-based Drosophila melanogaster model to investigate copper-induced toxicity with emphasis on glial-associated neurodegenerative mechanisms. The CuO NP of average size of -88 nm was synthesised in-house and exposed to flies through oral mode. The locomotor abnormality was investigated in larvae and adults, indicating neuronal dysfunction at both early and late developmental stages. Propidium iodide and 4',6-diamidino-2-phenylindole staining confirmed early cellular damage in the eye-antennal imaginal disc of the 3rd instar larvae. Scanning electron microscope - energy-dispersive X-ray spectroscopy analysis revealed the copper deposition in the gut and brain of the third instar larvae, which confirms the systemic uptake. The markers of genotoxic stress are the increased levels of reactive oxygen species and micronuclei formation in gut epithelial cells, while reduced pupal count is an indicator of developmental impairment due to copper toxicity. Compromised neuroglial interactions were evidenced by cone cell abnormalities and photoreceptor degeneration in pupae and adults. Moreover, the alterations of the acetylcholinesterase (AchE) activity indicated an impairment of the cholinergic neurotransmission. In conclusion, the results indicate that dietary exposure to CuO NP induces oxidative stress, developmental defects, and glial-related neurodegenerative changes. The results establish the fruit fly as a relevant in vivo model for the study of CuO NP toxicity and related neurologic disorders.