STRUCTURAL ALTERATIONS OF THE HIPPOCAMPAL-FORMATION OF ADRENALECTOMIZED RATS - AN UNBIASED STEREOLOGICAL STUDY

Previous studies have demonstrated that adrenalectomy rapidly induces cell death in hippocampal formation. However, these previous studies h ave involved only qualitative observations or biased estimates. Theref ore, the selectivity of the effects of adrenalectomy and the magnitude of changes occurring, remain controversial. The present work employed unbiased stereological tools to examine the effects of adrenalectomy on the number of neurons in, and the volume of, the hippocampal format ion. Male rats were adrenalectomized 15, 30 or 120 days before sacrifi ce at 180 days of age. The total number of neurons in the somal layers and hilus of the hippocampal formation was estimated using the optica l fractionator. The volume of the different layers of each subdivision in the hippocampal formation was determined according to the Cavalier i principle. A progressive reduction, reaching 43%, was found in the t otal number of granule cells. Adrenalectomized animals exhibited a red uction in the volume of all layers of the dentate gyrus. No other regi on of the hippocampal formation displayed significant cell loss or a r eduction in volume. In addition, the main neuronal subpopulations of t he dentate gyrus were also evaluated, and a reduction in the total num ber of GABA- and neuropeptide Y-immunoreactive neurons in the molecula r and granule cell layers of adrenalectomized rats was found. No quant itative changes were observed in the hilus. To characterize the glial response to the neuronal degeneration, we estimated the total number o f cells immunoreactive for glial fibrillary acidic protein in the dent ate gyrus. Although no variation in the total number of glial cells wa s found, signs of astroglial activation were observed in the adrenalec tomized group. The present data strengthen the evidence pointing to th e critical role of corticosteroids in maintaining the structural integ rity of the der;tate gyrus.