Necrostatin-1 Relieves Learning and Memory Deficits in a Zebrafish Model of Alzheimer’s Disease Induced by Aluminum
NEUROTOXICITY RESEARCH(2022)
摘要
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.
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关键词
Alzheimer’s disease,Aluminum,Zebrafish,Necroptosis,Necrostatin-1
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