Effects of Aluminum Administration on The Structure of The Principal Cells of The Hippocampus in The Adult Albino Rats and The Possible Protective Role of Lithium

Background: Concerns are raised about a link between increased levels of aluminum in drinking water and Alzheimer's disease. Excessive aluminum exposure has been shown to reduce the intrinsic electrical activity of the hippocampal neurons. Recently, it was reported that lithium salts which are frequently used as an effective drug for the treatment of several psychiatric disorders in humans, also possess  neuroprotective properties. Aim of  the Work: This study was conducted to demonstrate the aluminum–induced changes in the structure of the principal cells of the dentate gyrus, CA3, and CA1 fields of the hippocampus in rats and to study the role of lithium in their protection. Materials and Methods: A total of 36 adult male albino rats were divided into 4 groups Group I (12 rats) was  the  controls, Group II (8 rats) treated with aluminum chloride in a dose of 200 mg/kg BWT orally once daily for 2 months. Group III consisted of 8 rats, treated with lithium chloride in a dose of 1mmol/kg BWT daily via intraperitoneal injection for 2 months. Group IV consisted of 8 rats treated with both aluminum chloride and lithium chloride in the same dose, duration, and mode of administration as in groups II and III. After 2 month rats were sacrificed and brains were extracted from the skull. The hippocampi of 5 brains in each group were dissected out, divided into septal, middle and temporal portion and placed in 5% cacodylate buffered gluteraldehyde solution over night at 4°C. Thereafter were processed to study with transmission electron microscope, Semi-thin sections were stained with toluidine blue and ultra-thin sections (450 - 500A) were stained with uranyl acetate and lead citrate. Stained ultrathin sections were examined electron microscopy. Another 3 brains in each group were processed to be studied by Golgi-cox method. In addition, 4 brains of control rats were processed to be studied by Einarson's Gallocyanin stain. The number of the principal cells in the dentate gyrus, CA3 and CA1 fields of the hippocampus were measured in all the studied groups and statistically analyzed. Results: The principal cells of three studied hippocampal regions in the aluminum-treated rats showed degenerative changes. Ultrastructural study revealed that these changes involved both the nuclei and the cytoplasmic organelles. The cytoplasm of  the cells had many vacuoles, lysosomes and damaged mitochondria with marked decrease of the ribosomes as well as rough endoplasmic reticulum, in addition to the presence of nuclear chromatin condensation. Besides, an apparent decrease occurs in the amount of synaptic vesicles in the presynaptic terminals, and Golgi stain showed apparent decrease in the extent and branching of the dendrites of the neurons with partial loss of the spines. Morphometric study demonstrated a significant decrease in the number of the principal cells in the various hippocampal regions as compared with the control. In the group of rats treated with both aluminum and lithium, fine structural study of the principal cells showed normal appearance of the nuclei and the cytoplasmic organelles. Some vacuoles were still observed in the cytoplasm. Lithium can attenuate the reduction in the extent and branching of the dendrites of the principal hippocampal neurons resulting from the aluminum treatment. Morphometric study demonstrated that lithium reduced the aluminum-induced cell loss in the principal cells in the various hippocampal regions particularly in the dentate gyrus. Conclusions: Aluminum induce changes in the structure of the principal cells of the dentate gyrus, CA3, and CA1 fields of the hippocampus in rats. Lithium might play an important role in the protection of the hippocampus from aluminum-induced neuronal damage and cell loss.