Aluminium toxicity in the rat brain: histochemical and immunocytochemical evidence.
Although the neurotoxic actions of aluminium (Al) have been well documented, its contribution to neurodegenerative diseases such as Alzheimer's disease remains controversial. In the present study, we applied histochemical techniques to identify changes induced by intracerebroventricular Al injections (5.4 microg in 5.5 microl, daily over a period of 5 successive days) in the adult rat brain after survival periods of either 1 or 6 weeks. For both Al- and saline-infused controls, no major signs of gross histological changes were evident in cresyl violet-stained sections. Al (as indicated by the fluorescent Morin staining) was concentrated in white matter of the medial striatum, corpus callosum, and cingulate bundle. Immunoreactivity of astrocytes and phagocytic microglia based on glial fibrillary acidic protein and ED1 markers, respectively, revealed a greater inflammatory response in Al-injected animals compared to controls. Damage of the cingulate bundle in Al-treated 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 may cause learning and memory deficits, and contribute to pathological processes in Alzheimer's disease.
Platt
B
B
Biomedical Sciences, Aberdeen University, Scotland, Aberdeen, UK. b.platt@abdn.ac.uk
Fiddler
G
G
Riedel
G
G
Henderson
Z
Z
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000535:Aluminum / Q000493:pharmacokinetics / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000493:pharmacokinetics; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D007202:Indicators and Reagents / Q000493:pharmacokinetics; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D047309:Flavones
D000109:Acetylcholine; D000110:Acetylcholinesterase; D000535:Aluminum; D002795:Choline O-Acetyltransferase; D005419:Flavonoids; D005904:Glial Fibrillary Acidic Protein; D005968:Glutamate Decarboxylase; D007202:Indicators and Reagents; D009498:Neurotoxins; C008548:morin; D047309:Flavones