Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain
Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain
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DOI：
10.1002/jnr.10877
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发表时间：
2004-02-15
影响因子：
4.2
通讯作者：
Bondy, SC
中科院分区：
文献类型：
--
作者：
Campbell, A;Becaria, A;Bondy, SC
铝 (Al) 暴露与年龄相关神经系统疾病之间的联系早已被提出。尽管金属影响疾病过程的确切机制尚不清楚，但有证据表明接触铝会导致氧化应激和炎症事件增加。这些过程也被认为在阿尔茨海默病 (AD) 中发挥着一定作用，接触金属可能会加剧这些事件，从而导致这种疾病。饮用水中的乳酸铝（0.01、0.1 和 1 mM）持续 10 周会增加小鼠大脑中的炎症过程。这些水平中的最低水平是在住宅饮用水中金属浓度升高的地区发现增加AD患病率的范围内（Flaten [2001] Brain Res. Bull. 55:187-196）。接受治疗的动物大脑中核因子-κB、肿瘤坏死因子-α (TNF-α) 和白介素 1α (IL-1α) 水平均有所增加。治疗后 TNF-α 的 mRNA 也上调。在铝处理动物的纹状体中发现神经胶质原纤维酸性蛋白水平和反应性小胶质细胞的增强。暴露动物大脑中β淀粉样蛋白（Abeta(40)）的水平没有显着改变。由于在接受治疗的动物的血清或肝脏中没有观察到平行变化，因此金属的促炎作用可能对大脑具有选择性。铝暴露可能不足以直接导致老年斑主要成分的异常产生，但确实会加剧与大脑衰老相关的潜在事件，因此可能导致神经退行性病变的进展。 (C) 2004 Wiley-Liss, Inc.
A link between aluminum (Al) exposure and age-related neurological disorders has long been proposed. Although the exact mechanism by which the metal may influence disease processes is unknown, there is evidence that exposure to Al causes an increase in both oxidative stress and inflammatory events. These processes have also been suggested to play a role in Alzheimer's disease (AD), and exposure to the metal may contribute to the disorder by potentiating these events. Al lactate (0.01, 0.1, and 1 mM) in drinking water for 10 weeks increased inflammatory processes in the brains of mice. The lowest of these levels is in the range found to increase the prevalence of AD in regions where the concentrations of the metal are elevated in residential drinking water (Flaten [2001] Brain Res. Bull. 55:187-196). Nuclear factor-kappaB as well as tumor necrosis factor-alpha (TNF-alpha) and interleukin 1alpha (IL-1alpha) levels were increased in the brains of treated animals. The mRNA for TNF-alpha was also up-regulated following treatment. Enhancement of glial fibrillary acidic protein levels and reactive microglia was seen in the striatum of Al-treated animals. The level of amyloid beta (Abeta(40)) was not significantly altered in the brains of exposed animals. Insofar as no parallel changes were observed in the serum or liver of treated animals, the proinflarnmatory effects of the metal may be selective to the brain. Al exposure may not be sufficient to cause abnormal production of the principal component of senile plaques directly but does exacerbate underlying events associated with brain aging and thus could contribute to progression of neurodegeneration. (C) 2004 Wiley-Liss, Inc.