Neurotoxicity of aluminum oxide nanoparticles and their mechanistic role in dopaminergic neuron injury involving p53-related pathways
2020
Liu, Huanliang | Zhang, Wei | Fang, Yanjun | Yang, Honglian | Tian, Lei | Li, Kang | Lai, Wenqing | Bian, Liping | Lin, Bencheng | Liu, Xiaohua | Xi, Zhuge
The central nervous system is a potential target for Al₂O₃ nanoparticles (Nano-Al₂O₃). Here, we investigated the effects of intranasal instillation of Nano-Al₂O₃ on the distribution and damage in crucial functional sub-brain regions of rats. In vivo results show that Nano-Al₂O₃ was translocated into the brain via the olfactory nerve pathway. Nano-Al₂O₃ accumulated in the hippocampus, olfactory bulb, cerebral cortex, and striatum, causing ultrastructural changes, oxidative damage, inflammatory responses, and histopathological damage in sub-brain regions. As indicated by in vitro studies, cell viability decreased with the addition of Nano-Al₂O₃, which increased the levels of lactate dehydrogenase and oxidative stress. Nano-Al₂O₃ also impaired mitochondrial function, disturbed the cell cycle and induced apoptosis. In addition, Nano-Al₂O₃ decreased the expression of cyclin D1, bcl-2, Mdm2, and phospho-Rb and increased the expression of p53, p21, Bax, and Rb. Therefore, oxidative stress, mitochondrial dysfunction, and p53-related pathways might be important in the process of dopaminergic neurotoxicity induced by Nano-Al₂O₃. The current study establishes a striatum damage model and identifies molecular biomarkers of dopaminergic neuron damage induced by Nano-Al₂O₃. In brief, our study demonstrates that Nano-Al₂O₃ exposure can be a risk factor for neurodegenerative diseases and may negatively impact the hippocampus, striatum, and dopaminergic neurons.
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