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 t he hippocampal formation. However, recent studies have strongly challe nged this view. In order to clarify this issue, we have employed for t he first time the optical fractionator and the Cavalieri principle, tw o unbiased stereological tools, to estimate respectively the total num ber of neurons and the volumes of the main subdivisions of the hippoca mpal formation of rats submitted to corticosterone treatment for diffe rent periods, either neonatally or in adulthood. A significant reducti on in the number of neurons and in the volumes of the layers of the de ntate gyrus and CA3 hippocampal field was found in rats exposed to glu cocorticoids 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. Co nversely, when the exposure occurred only during adulthood, no signifi cant neuronal loss was observed, but there were significant reductions in the volume of layers in the dentate gyrus and CA3 hippocampal fiel d. To search for signs of structural recovery, we incorporated a group of rats submitted to corticosterone treatment during the neonatal per iod in which the hormonal conditions were restored thenceforth. In thi s group we found a significant increase in the volume of the molecular layer of the dentate gyrus when compared with rats that were kept und er corticosteroid treatment. In conclusion, these data provide a sound structural basis for the cognitive deficits observed during, and foll owing, exposure to increased levels of glucocorticoids. (C) 1998 Elsev ier Science B.V. All rights reserved.