Necrostatin-1 Relieves Learning and Memory Deficits in a Zebrafish Model of Alzheimer's Disease Induced by Aluminum

Aluminum (Al) is considered one of the environmental risk factors for Alzheimer's disease (AD). The present study aims to establish a zebrafish AD model induced by Al and explore if necrostation-1 (Nec-1), a specific inhibitor of necroptosis, is effective in relieving learning and memory deficits in the zebrafish AD models. We treated adult zebrafish with aluminum trichloride at various doses for 1 month, followed by a T-maze test to evaluate learning and memory performance. Al concentration, levels of acetylcholine (Ach), and AD-related protein and gene expression in the brain tissue were evaluated in the zebrafish AD models. Our results demonstrated that in the brain tissue of Al-treated zebrafish, Al accumulated, Ach levels decreased, and AD-related genes and proteins increased. As a result, the learning and memory performance of Al-treated zebrafish was impaired. This suggested that a zebrafish AD model was established. To test the effect of Nec-1 on the zebrafish AD model, we added Nec-1 into the culture medium of the Al-treated adult zebrafish. The results demonstrated that Nec-1 could relive the learning and memory deficits, enhance Ach levels and the numbers of neural cells, and impact necroptosis-related gene expression. We concluded that Nec-1 could reverse Al-induced learning and memory impairment and had potential theoretical value in the zebrafish AD model.