Aluminum (Al) is ubiquitously present in the environment and known to be a neurotoxin for humans. The trivalent free Al anion (Al³⁺) can cross the blood-brain barrier (BBB), accumulate in the brain, and elicit harmful effects to the central nervous system (CNS) cells. Thus, evidence has suggested that Al increases the risk of developing neurodegenerative diseases, particularly Alzheimer’s disease (AD). Purinergic signaling has been shown to play a role in several neurological conditions as it can modulate the functioning of several cell types, such as microglial cells, the main resident immune cells of the CNS. However, Al effects on microglial cells and the role of the purinergic system remain elusive. Based on this background, this study is aimed at assessing the modulation of Al on purinergic system parameters of microglial cells. An in vitro study was performed using brain microglial cells exposed to Al chloride (AlCl₃) and lipopolysaccharide (LPS) for 96 h. The uptake of Al, metabolism of nucleotides (ATP, ADP, and AMP) and nucleoside (adenosine), and the gene expression and protein density of purinoceptors were investigated. The results showed that both Al and LPS increased the breakdown of adenosine, whereas they decreased nucleotide hydrolysis. Furthermore, the findings revealed that both Al and LPS triggered an increase in gene expression and protein density of P2X7R and A2AR receptors, whereas reduced the A1R receptor expression and density. Taken together, the results showed that Al and LPS altered the setup of the purinergic system of microglial cells. Thus, this study provides new insights into the involvement of the purinergic system in the mechanisms underlying Al toxicity in microglial cells.

中文翻译：

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铝诱导 BV-2 脑小胶质细胞嘌呤能系统参数的改变

铝 (Al) 普遍存在于环境中，并且已知是人类的神经毒素。三价游离铝阴离子（Al ³⁺) 可以穿过血脑屏障 (BBB)，在大脑中积聚，并对中枢神经系统 (CNS) 细胞产生有害影响。因此，有证据表明铝会增加患神经退行性疾病的风险，尤其是阿尔茨海默病 (AD)。嘌呤能信号已被证明在多种神经系统疾病中发挥作用，因为它可以调节多种细胞类型的功能，例如小胶质细胞，CNS 的主要驻留免疫细胞。然而，铝对小胶质细胞的影响和嘌呤能系统的作用仍然难以捉摸。基于此背景，本研究旨在评估铝对小胶质细胞嘌呤能系统参数的调节。的体外使用暴露于氯化铝脑小胶质细胞（进行研究的AlCl ₃) 和脂多糖 (LPS) 96 小时。研究了铝的摄取、核苷酸（ATP、ADP 和 AMP）和核苷（腺苷）的代谢，以及嘌呤受体的基因表达和蛋白质密度。结果表明，Al 和 LPS 都增加了腺苷的分解，而它们减少了核苷酸水解。此外，研究结果表明，A1 和 LPS 都引发了 P2X7R 和 A2AR 受体基因表达和蛋白质密度的增加，而降低了 A1R 受体的表达和密度。总之，结果表明Al和LPS改变了小胶质细胞嘌呤能系统的设置。因此，这项研究为嘌呤能系统参与小胶质细胞中铝毒性的机制提供了新的见解。