Chronic exposure to aluminum in drinking water increases inflammatory parameters selectively in the brain

Abstract

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 (Abeta40) 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 proinflammatory 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.

The Role of Mental and Physical Activities against Development of Alzheimer ’s Disease in Socialized and Isolated Rats

“…In agreement with the present results, previous studies indicate that Al can stimulate the production of proinflammatory cytokine [130]. The levels of activated NFκB, an immune related factor, were found to be significantly increased in the brains of mice treated with Al [131]. Activated NFκB has been shown to increase TNF-α synthesis [129].…”

Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration

“…However, other studies that better reflect common human exposures have been conducted using more extended treatment with lower levels of Al resembling those found in some water supplies or exposures more closely paralleling human intake. One such study using Al in the drinking water, found indications of heightened inflammatory activity within brain tissue (Campbell et al, 2004) such as elevated levels of pro-inflammatory cytokines, and nitric oxide synthetase. These changes were found after Al salts had been in the drinking water of mice for three months at concentrations below those found in some residential water supplies.…”

Is Encephalopathy a Mechanism to Renew Sulfate in Autism?

“…Both in vitro and in vivo evidence demonstrate that aluminum increases both glutamate levels and pro-inflammatory cytokines like TNF-alpha in the brain [149][150][151][152][153][154], thus promoting an encephalitic reaction cascade. Aluminum has been shown to facilitate increases in intracellular calcium and ROS that are induced by other neurotoxicants, such as glutamate and ferrous iron [155].…”