P. Fattoretti, C. Bertoni-Freddari, M. Balietti, B. Giorgetti, M. Solazzi, P. Zatta

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.

Keywords (Optional): 
Aluminum administration
brain metal ions
Timm's reaction
Alzheimer's disease