Cortisol reduces hippocampal glucose metabolism in normal elderly, but not in Alzheimer's disease
Cortisol reduces hippocampal glucose metabolism in normal elderly, but not in Alzheimer's disease
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DOI：
10.1210/jcem.82.10.4305
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发表时间：
1997-10-01
影响因子：
5.8
通讯作者：
McEwen, B
中科院分区：
文献类型：
--
作者：
deLeon, MJ;McRae, T;McEwen, B
已知糖皮质激素在外周葡萄糖动员和代谢的调节中起作用。虽然一些动物研究表明，海马葡萄糖代谢减少急性和慢性皮质酮的作用，过量的糖皮质激素是有害的海马神经元，很少有人知道糖皮质激素在人类的中枢作用。在这项研究中，我们研究了大脑葡萄糖利用（CMRglu）的反应氢化可的松（皮质醇）在7个正常老年人和8个阿尔茨海默病（AD）患者。在单独的2天，在推注35 mg氢化可的松或安慰剂后立即给予2-脱氧-2-[F-18]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。使用两种方法分析PET CMRglu图像：图像变换，允许在逐体素基础上对病例进行分析，以及基于解剖学的感兴趣区域方法，使用共配准磁共振成像扫描。两种图像分析方法产生了相似的结果，相对于安慰剂，识别出对氢化可的松激发的特定海马CMRglu减少，其仅限于正常组。感兴趣区域技术显示，CMRglu在右侧和左侧大脑中分别减少了16%和12%。PET扫描期间收集的血液显示，对于正常组，从氢化可的松给药后约25分钟开始血糖水平升高。而AD组则没有这种效果。AD组的基线皮质醇升高，但氢化可的松的清除率在两组之间没有差异。总之，这些数据表明，在正常个体中，在药理剂量的皮质醇的存在下，海马体的葡萄糖利用率特别降低，血清葡萄糖水平增加。基于哈特的其他研究，我们提供的解释是糖皮质激素介导的葡萄糖转运的调节在AD中改变，这可能是海马对皮质醇不敏感和这些患者未能建立外周葡萄糖反应的基础。由于我们的研究结果可以反映AD患者的状态改变，我们将我们的结果解释为AD代谢异常的初步证据。结果表明，氢化可的松的挑战作为海马反应性的测试继续研究。
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-[F-18]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 hart 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.