Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus.

In order to determine whether short-term glucocorticoid manipulations influence the morphology and survival of neurons in the adult mammalian hippocampal formation, we performed quantitative analyses of Golgi-impregnated and Nissl-stained tissue from the brains of sham operated male rats, adrenalectomized male rats and adrenalectomized male rats which received corticosterone replacement. Three days after adrenalectomy, massive cell death, as detected by a dramatic increase in number of pyknotic cells, was observed in the granule cell layer of the dentate gyrus. By seven days following adrenalectomy, the numbers of pyknotic cells were even greater. Moreover, significant decreases in cross-sectional cell body area and numbers of dendritic branch points of Golgi-impregnated dentate gyrus granule cells were detected at seven days after adrenalectomy. Replacement of corticosterone to adrenalectomized rats prevented the appearance of large numbers of pyknotic cells as well as the decrease in granule cell cross-sectional cell body area and the numbers of dendritic branch points. In contrast, no obvious signs of degeneration were detected in the pyramidal cell layers of the CA1 and CA3 regions of the hippocampus at either three or seven days following adrenalectomy. In addition, no significant changes in morphological characteristics were observed in CA1 or CA3 pyramidal cells with adrenalectomy. These results show that dentate gyrus granule cells require glucocorticoids for their survival and for the maintenance of normal morphology and suggest that granule cell morphology and/or survival may undergo constant fluctuation in response to diurnal rhythms or stress-induced changes in glucocorticoid levels.