TRIM24-DTNBP1-ATP7A mediated astrocyte cuproptosis in cognition and memory dysfunction caused by YO NPs.

Yttrium oxide nanoparticles (YO NPs), extensively utilized rare earth nanoparticles, exhibited a diverse range of applications across various fields, which leading to increased human exposure. Moreover, potential neurotoxic risks have been associated with their use, yet the underlying mechanism remains unclear. The present study aimed to investigate the effects of YO NPs on cognitive function in rats with a particular focus on elucidating the pivotal role played by astrocytes in this process. The results demonstrated that YO NPs induced cognitive and memory impairment in rats, copper (Cu) accumulation and cuproptosis of astrocytes as contributing factors. Furthermore, we elucidated that YO NPs induced astrocytes cuproptosis by inhibiting TRIM24/DTNBP1/ATP7A signaling pathway-mediated cellular Cu efflux. We provide, for the first time, the important involvement of astrocytes in YO NPs-induced neurotoxicity, elucidating that cuproptosis as the primary mode of cell death. These results offer valuable insights for the future safe application of rare earth nanoparticles in field of neurology.