Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Lucknow, Uttar Pradesh, India.
Toxicol Mech Methods. 2022 Oct;32(8):616-627. doi: 10.1080/15376516.2022.2058898. Epub 2022 Apr 7.
Aluminum is an environmentally abundant potential neurotoxic agent that may result in oxidative damage to a range of cellular biomarkers. The potential sources of aluminum accumulation in the body include drinking water, food, medicines, vaccines, and aluminum cookware utensils, etc. The accumulation of aluminum in the brain is reported to be associated with cholinergic dysfunction, oxidative stress and neuronal damage, which may ultimately cause Alzheimer's disease. Since chronic exposure to aluminum leads to its accumulation in the brain, so this study was done by a long-term (24 weeks) low dose (20 mg/kg) oral exposure of aluminum chloride in rats. In this chronic model, we have evaluated the major hallmarks of Alzheimer's disease including amyloid-beta (Aβ) and phosphorylated-tau (p231-tau) protein in brain tissue. Furthermore, we evaluated the level of acetyl cholinesterase activity, inflammatory cytokines such as TNF-α, IL-6 and IL-1β, and oxidative stress biomarkers in the rat brain in this model. The neurobehavioral parameters were also assessed in animals by using spontaneous locomotor activity, passive avoidance, rotarod test and novel object recognition test to evaluate alteration in learning, memory and muscle co-ordination. We found that chronic oral exposure to aluminum chloride causes a significant increase in structural hallmarks such as Aβ and p231-tau levels along with pro-inflammatory cytokines (TNF-α and IL-6), oxidative stress, and a decrease in antioxidant markers such as GSH and catalase in the brain tissue. These biomarkers significantly affected neurobehavioral parameters in animals. This study provides a mechanistic understanding of chronic aluminum-induced neuronal toxicity in the brain with relevance to Alzheimer's disease.
铝是一种环境中含量丰富的潜在神经毒性物质，可能导致一系列细胞生物标志物发生氧化损伤。体内铝积累的潜在来源包括饮用水、食物、药物、疫苗和铝制炊具等。据报道，铝在大脑中的积累与胆碱能功能障碍、氧化应激和神经元损伤有关，这可能最终导致阿尔茨海默病。由于慢性暴露于铝会导致其在大脑中积累，因此本研究通过长期（24 周）低剂量（20mg/kg）口服氯化铝对大鼠进行。在这种慢性模型中，我们评估了阿尔茨海默病的主要特征，包括脑组织中的淀粉样β（Aβ）和磷酸化tau（p231-tau）蛋白。此外，我们评估了该模型中大鼠大脑中乙酰胆碱酯酶活性、炎症细胞因子（TNF-α、IL-6 和 IL-1β）和氧化应激生物标志物的水平。通过自发运动活动、被动回避、旋转棒试验和新物体识别试验，还评估了动物的神经行为参数，以评估学习、记忆和肌肉协调能力的变化。我们发现，慢性口服氯化铝暴露会导致结构标志物（如 Aβ 和 p231-tau 水平）以及促炎细胞因子（TNF-α和 IL-6）、氧化应激显著增加，同时脑组织中的抗氧化标志物（GSH 和过氧化氢酶）显著减少。这些生物标志物显著影响了动物的神经行为参数。本研究提供了对与阿尔茨海默病相关的大脑中慢性铝诱导神经元毒性的机制理解。
