Size-dependent neurotoxicity of PbSe nanoparticles: Oxidative stress, apoptosis, and synaptic dysfunction mediate cognitive impairment in rats

Lead selenide nanoparticles (PbSe-NPs) have drawn increasing attention because of their great application potential in various fields, yet their potential neurotoxicity remains unreported. In this study, biomedical exposure to PbSe-NPs via intraperitoneal injection was simulated, and the in vivo damage caused by 30-nm and 70-nm PbSe-NPs to the rat central nervous system and their in vitro adverse effects on primary hippocampal neuron plasticity were explored. Following the treatment of rats with 10 mg/kg PbSe-NPs or 0.02 mg/kg Pb²⁺ once weekly for 8 weeks, 30 nm PbSe-NPs crossed the blood–brain barrier (BBB), accumulated in the hippocampus, and further impaired cognitive and memory functions. In addition, 30-nm PbSe-NPs caused the accumulation of reactive oxygen species (ROS), increased the levels of lipid peroxidation products, and increased the levels of apoptosis-related proteins and inflammatory cytokines in the hippocampus. However, 70 nm PbSe-NPs and 0.02 mg/kg Pb²⁺ did not induce the above phenomena. Interestingly, in in vitro experiments, both sizes of PbSe-NPs could damage primary cultured hippocampal neurons and induce apoptosis, but their effects did not significantly differ. Moreover, PbSe-NPs downregulated the expression of synapse-related proteins, thereby affecting the synaptic plasticity of neurons, whereas Pb²⁺ released from PbSe-NPs did not cause this adverse effect. The in vitro results in primary neurons confirmed that 30 nm PbSe-NPs have direct neurotoxic effects and impair neuronal function, which is consistent with the cognitive impairment observed in vivo. This study provides a reference for the risk assessment and scientific supervision of PbSe-NPs in biomedical applications.