Effect of long term hydergine treatment on the age-dependent loss of mossy fibers and of granule cells in the rat hippocampus

The effects of senescence and of long-term Hydergine treatment on the density and pattern of mossy fibers and on the number of granule cells of the dentate gyrus were studied in the rat hippocampus. Timm's technique for the histochemical demonstration of tissue stores of zinc, associated with quantitative image analysis and microdensitometry, was used for the study of mossy fibers. Consistent with our previous studies, we observed an age-related reduction both in the area occupied by mossy fibers and in the intensity of Timm staining in the mossy fiber area. Moreover, the density of granule cells in the dentate gyrus of hippocampus was reduced with age. Hydergine administration (1 and 3 mg/kg/day, p.o.), started when the rats were 17 months old and continued for 4 months, significantly increased the area occupied by mossy fibers and the intensity of Timm staining in the hippocampus of senescent animals. Moreover, Hydergine treatment was found to counteract the age-dependent decrease in granule cell number in the dentate gyrus of the hippocampus. These findings suggest that treatment with Hydergine is effective in counteracting or in slowing down the morphological disorganization observable in the hippocampal formation with advancing age. Moreover, it is possible that the effects of Hydergine administration in elderly patients might be related to an effect at the level of the hippocampus.