GLUCOCORTICOID REGULATION OF MEMORY PERFORMANCE IN AGING HUMANS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。已知糖皮质激素（GC）调节脑代谢、生理和基因表达，特别是在海马中，以及整个动物的记忆功能。各种GC，包括内源性人GC皮质醇，可以以可逆的方式剂量和时间依赖性地降低人类记忆。这些结果与医源性GC暴露和应激相关的神经精神疾病有关。此外，最近对老年人的研究表明，与年龄相关的皮质醇水平的增加与年龄相关的记忆力下降有关。基于这些关联，本申请提出现在使用受控实验设计来测试GC暴露对老年人的直接影响，以便可以定义年轻人和老年人中显著影响的"剂量"阈值。这一知识对于识别有记忆障碍风险的个体以及最终预防这种影响的治疗考虑至关重要（例如，GC受体拮抗剂或钙通道阻滞剂）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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).