With the development of green energy technology, the Nickel (Ni)0.8Cobalt(Co)0.1Manganese(Mn)0.1(OH)₂ (NCM811) precursor has been used as a cathode material for lithium batteries due to its high energy density. However, this raises a concern about the risk of NCM811 exposure during raw material processing, battery production, and recycling. This study aimed to investigate the neurotoxic effects of NCM811 particle exposure and the underlying mechanism. C57BL/6J mice were intranasally exposed to NCM811 particles. Then, spatial memory ability was assessed using the Morris water maze. Metal accumulation and distribution in brain regions were analyzed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and histopathological changes were examined by histological staining. The proportion of peripheral T helper type 17 (Th17) cells was measured by flow cytometry, and the concentration of IL-17A in brain tissue was determined by ELISA. The effect of IL-17A on microglia was further verified in il17ra knockout mice. Furthermore, an agonist of the cAMP pathway was administered to examine its protective effects against NCM811 exposure. NCM811exposure resulted in spatial memory impairment in mice, accompanied by increased Mn²⁺ deposition in the hippocampus and microglial M1 polarization. NCM811 exposure also increased the proportion of Th17 cells in the periphery, accompanied by enhanced Th17 cell infiltration and elevated IL-17A levels in brain tissues. Mechanistically, IL-17A activated microglia via the IL-17RA, suppressed the cAMP-CREB pathway, and promoted M1 polarization, subsequently leading to aberrant synaptic pruning and neurotransmitter dysregulation. Administration of a cAMP agonist blocked microglial M1 polarization induced by NCM811. Il17ra knockout mice effectively resisted these neural effects. Our findings elucidate a novel mechanism by which NCM811 induces neurotoxicity through Th17 cell-mediated microglial polarization, providing potential therapeutic targets for cognitive dysfunction associated with battery material exposure in the context of green energy and sustainable development.
Dong et al. (Fri,) studied this question.