CHRONIC AIF(3) ADMINISTRATION .2. SELECTED HISTOLOGICAL OBSERVATIONS

Male Long-Evans rats were divided into four groups based on the concen trations of the AlF3 in the drinking water: 0.5 ppm, 5.0 ppm, 50 ppm, or a control solution of double-distilled, de-ionized water. Water was available ad libitum for 45 weeks. Following the behavioral studies, histological, immunohistochemical, and overall brain aluminum (Al) eva luations were made on portions of the brains from these animals. Selec ted coronal sections were stained by the Bielschowsky silver stain met hod, the Morin Al-fluorescence procedure, several standard neurohistol ogical methods for cellular proteins, and through the use of several i mmunohistochemical methods, including ones that reveal neurofilaments and reactive astrocytes (GFAP). This report presents descriptions of t he responses of the brains to the toxin exposure in regard to cell los s and other changes in the neocortex and hippocampus. The brain sectio ns were immunohistochemically studied using antibodies both to neurofi lament and phosphorylated neurofilament proteins. The three AlF3 group s did not differ from each other in overall brain Al content, but all treated groups had about twice the Al levels as did the control group. There were significant reductions in the number of neurons in the hip pocampal CA1 and CA3 areas of the AlF3 treated groups. In addition the cells of the hippocampal formation appeared disorganized and many cel ls in all subdivisions stained excessively for Nissl-like proteins and that may reflect cellular dysfunction. Cells in the outer layers of t he neocortex of the AlF3 groups exhibited darker Nissl staining and we re more argentophilic than cells in similar areas from brains of the c ontrols. These intracellular accumulations were not associated with in creases in either phosphorylated or non-phosphorylated protein. Reduce d numbers of cells evidencing neurofilament reaction product were foun d selectively in neocortical layer 4. There were large numbers of GFAP -positive cells in the brains of rats from all groups but the number o f reactive cells was not greater in the treated animals than in the co ntrols.