Chronic aluminum administration to old rats results in increased levels of brain metal ions and enlarged hippocampal mossy fibres
P. Fattoretti, C. Bertoni-Freddari, M. Balietti, B. Giorgetti, M. Solazzi, P. Zatta
Neurobiology of Aging Laboratory, INRCA Research Department, Via Birarelli 8, 60121 Ancona, Italy
The effect of chronic aluminium intake has been investigated in the
central nervous system of aged male Wistar rats to assess the potential
role of the accumulation of this metal ion on the development of
neurodegenerative features observed Alzheimer's disease. Aluminum
dichloride hexahydrate (2g/L) was administered for 6 months in the
drinking water. The content of Al3+, Cu2+, Zn2+ and Mn2+ (mg/g fresh
tissue) was measured by inductively coupled plasma atomic emission
spectrometer (ICP-AES) in the prosencephalon + mesencephalon,
pons-medulla and cerebellum of aged control and Al(III)-treated
animals. The area occupied by the mossy fibres in CA3 field of the
hippocampus was estimated by computer-assisted morphometric methods
following Timm's preferential staining. In aged Al(III)-treated rats
the contents of Al3+, Cu2+, Zn2+ and Mn2+ were significantly increased
both in prosencephalon + mesencephalon and pons-medulla, while no
change was observed in the cerebellum except a decrease of Cu2+ in the
Al(III)-treated rats. The area occupied by the mossy fibres in the
hippocampal CA3 field was significantly increased (+32%) in aged
Al(III)-treated rats. Since Cu2+, Zn2+ and Mn2+ are contained in the
cytosolic and mitochondrial superoxide dismutases, we interpret the
increased content of these ions in aged Al(III)-treated rats to
represent an increased amount (genetic expression) of these antioxidant
enzymes. Considering that the positivity to Timm's reaction is based on
the presence of free or loosely bound Zn2+ ions within synaptic
terminals and that Zn2+ ions are reported to be accumulated by
hippocampal neurons when tissue injury occurs, the increased area of
the mossy fibres in CA3 field of old Al(III)-treated rats support an
increased hippocampal damage in these animals. Taken together, the
present findings document that the aging CNS is particularly
susceptible to Al(III) toxic effects which may increase the cell load
of oxidative stress and contribute as an aggravating factor to the
development of neurodegenerative events as observed in Alzheimer's
disease.
Key words:
Aluminum administration, brain metal ions, hippocampus, Timm's reaction, Alzheimer's disease
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