The neurotoxicity of environmental aluminum is still an issue

Abstract

Evidence for the neurotoxicity of extended exposure to low levels of aluminum salts is described using an animal model treated with aluminum at low levels reflecting those found in some water supplies. Emphasis is given to the potential role of aluminum in acceleration and promotion of some indices characteristic of brain aging. These hallmarks include the appearance of excess levels of inflammation in specific brain areas. Aluminum salts can increase levels of glial activation, inflammatory cytokines and amyloid precursor protein within the brain. Both normal brain aging and to a greater extent, Alzheimer's disease are associated with elevated basal levels of markers for inflammation. These are not attributable to obvious exogenous stimuli and may reflect the lifespan history of the organism's immune responses. It is possible that aluminum salts can act as a subtle promoter of such apparently unprovoked responses.

Fig. 1

Immunofluorescent staining for GFAP in the periventricular area. Sections derived from: control animals (A), Al exposed mice (B), mice treated with MPTP (C) and mice dosed with both Al and MPTP (D). Bars represent 100 microns. Each section derived from a representative mouse from a group of 3 receiving identical treatment.

Fig. 2

A. Northern blot of TNF-α in the brain of Al-exposed mice. β-actin was used to insure equal loading of all samples. Integrated density of the blots. β-actin intensity was used to adjust the values. B. Levels of TNF-α in the cytoplasmic fraction of the brain after treatment with Al. Bars represent mean of 6 individual determinations ± SE. *: Value is significantly different (p < 0.05) from the control.

Fig. 3

Cortical APP concentration in mice receiving 0, 10, or 100 mM Al lactate in drinking water. Bars represent mean of 6 individual determinations ± SE. * = different (p < 0.05) from the control.

Fig. 4

Microglial activation in the brain of Al lactate-exposed animals. (A) Control, (B) Al lactate (0.01 mM), (C) Al (0.1 mM), FC = Frontal cortex, CC = corpus callosum, CN/P = caudate nucleus/putamen, GP = globus pallidus. 20x magnification.