de Leon M J, McRae T, Rusinek H, Convit A, De Santi S, Tarshish C, Golomb J, Volkow N, Daisley K, Orentreich N, McEwen B
Department of Psychiatry, New York University Medical Center, New York 10016, USA.
J Clin Endocrinol Metab. 1997 Oct;82(10):3251-9. doi: 10.1210/jcem.82.10.4305.
Glucocorticoids are known to play a role in the regulation of peripheral glucose mobilization and metabolism. Although several animal studies have shown that hippocampal glucose metabolism is reduced acutely and chronically by the action of corticosterone and that excess glucocorticoids are harmful to hippocampal neurons, little is known about the central effects of glucocorticoids in the human. In this study we examined the brain glucose utilization (CMRglu) response to hydrocortisone (cortisol) in seven normal elderly and eight Alzheimer's disease (AD) patients. On 2 separate days, immediately after the administration of a bolus of either 35 mg hydrocortisone or placebo, we administered 2-deoxy-2-[18F]fluoro-D-glucose. After a 35-min radiotracer uptake period, positron emission tomography (PET) images were collected. PET CMRglu images were analyzed using two methods: an image transformation that allowed analyses across cases on a voxel by voxel basis, and an anatomically based region of interest method that used coregistered magnetic resonance imaging scans. Both image analysis methods yielded similar results, identifying relative to placebo, a specific hippocampal CMRglu reduction in response to the hydrocortisone challenge that was restricted to the normal group. The region of interest technique showed CMRglu reductions of 16% and 12% in the right and left hippocampi, respectively. Blood collected during the PET scans showed, for the normal group, a rise in plasma glucose levels, starting approximately 25 min after hydrocortisone administration. The AD group did not show this effect. Baseline cortisol was elevated in the AD group, but the clearance of hydrocortisone was not different between the groups. In conclusion, these data show that among normal individuals in the presence of a pharmacological dose of cortisol, the glucose utilization of the hippocampus is specifically reduced, and serum glucose levels increase. Based in part on other studies, we offer the interpretation that glucocorticoid-mediated regulation of glucose transport is altered in AD, and this may underlie both the hippocampal insensitivity to cortisol and the failure in these patients to mount a peripheral glucose response. As our findings could reflect an altered state of the AD patients, we interpret our results as preliminary with respect to evidence for metabolic abnormalities in AD. The results suggest the continued study of the hydrocortisone challenge as a test of hippocampal responsivity.
已知糖皮质激素在调节外周葡萄糖动员和代谢中发挥作用。尽管多项动物研究表明，皮质酮的作用会使海马体葡萄糖代谢急性和慢性降低，且过量的糖皮质激素对海马体神经元有害，但关于糖皮质激素在人体中的中枢作用却知之甚少。在本研究中，我们检测了7名正常老年人和8名阿尔茨海默病（AD）患者对氢化可的松（皮质醇）的脑葡萄糖利用率（CMRglu）反应。在2个不同的日子里，在静脉注射35mg氢化可的松或安慰剂后，我们立即给予2-脱氧-2-[18F]氟-D-葡萄糖。在35分钟的放射性示踪剂摄取期后，收集正电子发射断层扫描（PET）图像。PET CMRglu图像使用两种方法进行分析：一种图像转换方法，允许逐体素对病例进行分析；另一种基于解剖学感兴趣区域的方法，使用配准的磁共振成像扫描。两种图像分析方法得出了相似的结果，相对于安慰剂，发现正常组对氢化可的松激发的反应存在特定的海马体CMRglu降低。感兴趣区域技术显示，右侧和左侧海马体的CMRglu分别降低了16%和12%。PET扫描期间采集的血液显示，对于正常组，血浆葡萄糖水平在氢化可的松给药后约25分钟开始升高。AD组未显示出这种效应。AD组的基线皮质醇升高，但两组之间氢化可的松的清除率没有差异。总之，这些数据表明，在存在药理剂量皮质醇的正常个体中，海马体的葡萄糖利用率会特异性降低，血清葡萄糖水平会升高。部分基于其他研究，我们认为AD中糖皮质激素介导的葡萄糖转运调节发生了改变，这可能是海马体对皮质醇不敏感以及这些患者外周葡萄糖反应失败的基础。由于我们的发现可能反映了AD患者的改变状态，就AD代谢异常的证据而言，我们将我们的结果解释为初步的。结果表明，继续研究氢化可的松激发作为海马体反应性的测试。
