Effects of corticosterone treatment and rehabilitation on the hippocampal formation of neonatal and adult rats. An unbiased stereological study

Elevations in the plasma levels of glucocorticoids are associated with cognitive impairments that have been ascribed to loss of neurons in the hippocampal formation. However, recent studies have strongly challenged this view. In order to clarify this issue, we have employed for the first time the optical fractionator and the Cavalieri principle, two unbiased stereological tools, to estimate respectively the total number of neurons and the volumes of the main subdivisions of the hippocampal formation of rats submitted to corticosterone treatment for different periods, either neonatally or in adulthood. A significant reduction in the number of neurons and in the volumes of the layers of the dentate gyrus and CA3 hippocampal field was found in rats exposed to glucocorticoids in the neonatal period; furthermore, animals treated with corticosterone from birth until 180 days of age had also a reduction in the volume of the stratum radiatum of the CA1 hippocampal field. Conversely, when the exposure occurred only during adulthood, no significant neuronal loss was observed, but there were significant reductions in the volume of layers in the dentate gyrus and CA3 hippocampal field. To search for signs of structural recovery, we incorporated a group of rats submitted to corticosterone treatment during the neonatal period in which the hormonal conditions were restored thenceforth. In this group we found a significant increase in the volume of the molecular layer of the dentate gyrus when compared with rats that were kept under corticosteroid treatment. In conclusion, these data provide a sound structural basis for the cognitive deficits observed during, and following, exposure to increased levels of glucocorticoids. (C) 1998 Elsevier Science B.V. All rights reserved.