The Physiological Relevance of Glucocorticoid Endangerment of the Hippocampus a

A theme that permeates the papers in this volume is the deleterious nature of glucocorticoid (GC) excess. Sometimes the adverse effects of the steroid are implied indirectly. For example, when considering the extraordinary complexity of the regulation of GC secretion (see the paper by Dallman, for example), one is reminded of the need for such tight control-i.e., the pathologic consequences when such regulation fails. Or one must consider the catabolic effects of GCs when asking what the ultimate purpose is of GC secretion in response to stress (as in the work of Munck). Other papers consider the pathogenic consequences of GCs more directly. One of the most striking examples of such pathogenicity is the ability of GCs and of stress to damage the hippocampus, a structure in the limbic system of the brain that is critical to learning and memory. Moreover, GCs are able to endanger the hippocampus, impairing its capacity to survive a variety of coincident neurological insults. Such GC neurotoxicity and neuroendangerment have become relevant to understanding aspects of neural development (see the paper by Meaney), brain aging (see Landfield), a number of neuropsychiatric and endocrine disorders (see Gottfries), as well as some of the most common neurological diseases that damage the hippocampus. In this paper, 1 review the current knowledge concerning the cellular and molecular mechanisms by which GCs endanger the hippocampus. Most of these findings emerged only just recently, and they make it possible to begin asking some rather subtle questions about the phenomenon. I shall emphasize two such questions: a) Do GC endanger the hippocampus under physiological, as well as pharmacological circumstances? b) Are the mechanisms by which GCs act over the course of hours to days to endanger the hippocampus during a neurological insult related to the mechanisms by which GCs act over the course of weeks to months to directly damage the aging hippocampus?