Aluminium toxicity in the rat brain: Histochemical and immunocytochemical evidence

Although the neurotoxic actions of aluminium (At) have been well documented , its contribution to neurodegenerative diseases such as Alzheimer's diseas e remains controversial. In the present study, we applied histochemical tec hniques to identify changes induced by intracerebroventricular Al injection s (5.4 mug in 5.5 mul, daily over a period of 5 successive days) in the adu lt rat brain after survival periods of either 1 or 6 weeks. For both Al- an d saline-infused controls, no major signs of gross histological changes wer e evident in cresyl violet-stained sections. Al (as indicated by the fluore scent Morin staining) was concentrated in white matter of the media[ striat um, corpus callosum, and cingulate bundle. Immunoreactivity of astrocytes a nd phagocytic microglia based on glial fibrillary acidic protein and EDI ma rkers, respectively, revealed a greater inflammatory response in Al-injecte d animals compared to controls. Damage of the cingulate bundle in Al-treate d animals led to a severe anterograde degeneration of cholinergic terminals in cortex and hippocampus, as indicated by acetylcholinesterase labelling. Our data suggest that the enhancement of inflammation and the interference with cholinergic projections may be the modes of action through which Al m ay cause learning and memory deficits, and contribute to pathological proce sses in Alzheimer's disease. (C) 2001 Elsevier Science Inc.