Glucocorticoids (GCs) are know to regulate brain metabolism, physiology and gene expression, particularly in the hippocampus, as well as memory function in whole animals. Various GCs, including the endogenous human GC cortisol, can dose-and time-dependently decrease human memory in a reversible manner. These results are relevant to both iatrogenic GC exposure and stress-related neuropsychiatric conditions. In addition recent studies in aging humans suggest that age-related increases in cortisol levels are associated with progressice age-related memory declines. Based on these associations, this application proposes to now test the direct effect of GC exposure on older humans using a controlled experimental design so that the """"""""dose"""""""" threshold for significant effects in younger and older humans can be defined. This knowledge is critical to the identification of individuals at risk for memory impairment and ultimately to treatment considerations for the prevention of this effect (e.g., GC receptor antagonists or calcium channel blockers).
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