Chronic oral exposure of aluminum chloride in rat modulates molecular and functional neurotoxic markers relevant to Alzheimer’s disease

IF 2.8 4区 医学 Q2 TOXICOLOGY
M. Dey, R. Singh
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引用次数: 1

Abstract

Abstract 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 (Aβ1–42) 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 Aβ1–42 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.
大鼠慢性口服氯化铝暴露可调节与阿尔茨海默病相关的分子和功能神经毒性标志物
摘要铝是一种环境丰富的潜在神经毒性物质,可能对一系列细胞生物标志物造成氧化损伤。铝在体内积聚的潜在来源包括饮用水、食物、药品、疫苗和铝制炊具等。据报道,铝在大脑中的积聚与胆碱能功能障碍、氧化应激和神经元损伤有关,最终可能导致阿尔茨海默病。由于长期接触铝会导致其在大脑中积累,因此这项研究是由一名长期(24 周)低剂量(20 mg/kg)经口暴露于大鼠中的氯化铝。在这个慢性模型中,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蛋白β(Aβ1-42)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、炎性细胞因子如TNF-α、IL-6和IL-1β以及氧化应激生物标志物的水平。动物的神经行为参数也通过自发运动活动、被动回避、旋转棒测试和新型物体识别测试来评估学习、记忆和肌肉协调的变化。我们发现,长期口服氯化铝会导致结构特征显著增加,如aβ1-42和p231 tau水平,以及促炎细胞因子(TNF-α和IL-6)、氧化应激,以及脑组织中抗氧化标志物(如GSH和过氧化氢酶)的减少。这些生物标志物显著影响动物的神经行为参数。这项研究提供了对铝诱导的大脑中与阿尔茨海默病相关的慢性神经元毒性的机制理解。
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来源期刊
自引率
3.10%
发文量
66
期刊介绍: Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.
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