Investigation of the Neurotoxicity Mechanisms of Ni in Rat Neocortical Neurons Through Transcriptome Analysis.

The cytotoxic effects of Ni released from nickel-based alloy implants on tissues have been a longstanding research focus in biocompatibility studies. However, investigations into the neurotoxicity of Ni remain relatively limited. Building on our previous findings that Ni can rapidly affect the excitability of neuronal networks, this study further investigated the neurotoxic effects of prolonged Ni exposure. First, the cytotoxicity effects of Ni on rat neocortical neurons in vitro were evaluated by MTT cell viability assay, and changes in the length of the axon initial segment of neurons caused by Ni exposure were quantified. Next, transcriptome sequencing was employed to identify differentially expressed genes (DEGs) induced by Ni treatment, and four DEGs-, , , and -were selected for qRT-PCR validation. The ATP content of neurons was measured to assess cellular energy metabolism under Ni influence. Finally, by comparing these experimental results with our previous findings, this study explored the neurotoxicity mechanisms of Ni and analyzed the correlation between its neurotoxicity and cytotoxicity. This study revealed that the neurotoxicity mechanisms of Ni are associated with the concentration of Ni and the duration of its action. When at low concentrations or with short exposure times, Ni suppresses the excitability of the neuronal networks by rapidly blocking Ca channels, whereas at high concentrations or with prolonged exposure, it further inhibits the network's excitability by activating the HIF-1α pathway and inducing obvious cytotoxicity.