Magri Flavia, Cravello Luca, Barili Luca, Sarra Serena, Cinchetti Wilma, Salmoiraghi Fabrizio, Micale Giuliana, Ferrari Ettore
UO of Internal Medicine and Endocrinology, IRCCS S. Maugeri Foundation, Pavia, Italy.
Aging Clin Exp Res. 2006 Apr;18(2):167-70. doi: 10.1007/BF03327435.
Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.
海马体在学习和记忆中起着至关重要的作用，尽管它具有显著的可塑性，但由于其高浓度的皮质类固醇受体，它对压力激素也特别敏感。事实上，肾上腺类固醇通过作用于兴奋性和长时程增强或抑制来调节海马体的可塑性。通过一种时间生物学方法，我们研究了临床健康的老年受试者以及年龄匹配的痴呆患者（包括退行性和血管性类型）的皮质醇和脱氢表雄酮（DHEAS）分泌情况。与年轻对照组相比，临床健康的老年受试者和痴呆患者，尤其是患有阿尔茨海默病（AD）的患者，夜间的皮质醇水平显著更高，即在HPA轴对刺激或抑制输入的最大敏感性时刻。同时，发现DHEAS分泌明显存在年龄和疾病依赖性降低。因此，与年轻对照组相比，健康老年受试者的皮质醇与DHEAS摩尔比显著更高，痴呆患者更是如此，并且与年龄和认知障碍显著相关。最后，肾上腺分泌模式的定量和定性变化与通过MRI测量的海马体体积下降显著相关。总之，多条证据表明压力激素在老年受试者认知障碍的发生和发展中具有致病作用。随之而来的海马体神经元损伤可能反过来导致HPA轴的持续激活以及下丘脑加压素和促肾上腺皮质激素释放激素表达的增加。
