Affiliations: [a] Neurobiology of Aging Laboratory, INRCA Research Department, Ancona, Italy | [b] Josef Stefan Institute, Ljubljana, Slovenia | [c] Division of Pathology and Brain Bank, General Hospital, Dolo-Venice, Italy | [d] CNR-Institute for Biomedical Technologies, Padova Unit “Metalloproteins”, Department of Biology, University of Padova, Padova, Italy
Correspondence:
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Corresponding author: Paolo Zatta, CNR-Institute for Biomedical Technologies, Padova Unit "Metalloprotein", University of Padova, Department of Biology, Viale G. Colombo, 3 35121 Padova, Italy. Tel.: +39 049 827 6331; Fax: +39 049 827 6330; E-mail: [email protected].
Abstract: The effect of chronic aluminum intake has been investigated in the brain of aged male Wistar rats to assess the potential role of the accumulation of this metal ion on the development of neurodegenerative features observed in Alzheimer's disease. AlCl3 × 6 H2O (2g/L) was administered to experimental animals for 6 months in the drinking water. The total content of Al (μg/g fresh tissue) was measured by inductively coupled plasma atomic emission spectrometry (ICP-AES), while the content of Cu, Zn and Mn was determined by flame AAS in the prosencephalon + mesencephalon, pons-medulla and cerebellum of control and Al(III)-treated animals. The area occupied by mossy fibres in the CA3 field of the hippocampus was estimated by a computer-assisted morphometric method following Timm's preferential staining. In Al(III)-treated rats the concentration of Cu, Zn and Mn did not increase significantly (p < 0.5) in prosencephalon + mesencephalon, nor in pons-medulla (p < 0.5) except for Cu (p < 0.05) in pons-medulla. In the cerebellum the only significant increase was seen for Zn (p < 0.01) while no change was observed for Cu and Mn. The area occupied by the mossy fibres in the hippocampal CA3 field was significantly increased (+32%) in aged Al(III)-treated rats. Since Cu, Zn and Mn are essential components of the cytosolic and mitochondrial superoxide dismutases, it is possible that the increased content of these ions in aged Al(III)-treated rats represents an increased amount of genetic expression of these antioxidant enzymes. Considering that the positivity to Timm's reaction is based on the presence of free or loosely bound Zn+2 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 Al(III)-treated rats could indicate increased hippocampal damage in these animals. Taken together, the present findings indicate that the aging CNS is particularly susceptible to Al(III) toxic effects which may increase the cell load of oxidative stress and may contribute, as an aggravating factor, to the development of neurodegenerative events as observed in Alzheimer's disease.
