Dey_2022_Toxicol.Mech.Methods__1

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 body include drinking water, food, medicines, vaccines, and aluminum cookware utensils etc. The accumulation of aluminum in brain is reported to be associated with cholinergic dysfunction, oxidative stress and neuronal damage, that may ultimately cause Alzheimer's disease. Since chronic exposure of aluminum leads to its accumulation in 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 (Abeta(1-42)) and phosphorylated-tau (p231-tau) protein in brain tissue. Furthermore, we evaluated the level of acetyl cholinesterase activity, inflammatory cytokines such as TNF-alpha, IL-6 and IL-1beta, and oxidative stress biomarkers in 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 of aluminum chloride causes a significant increase in structural hallmarks such as Abeta(1-42) and p231-tau levels along with proinflammatory cytokines (TNF-alpha 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 brain with relevance to Alzheimer's disease.