Schubert Mirjam I, Kalisch Raffael, Sotiropoulos Ioannis, Catania Caterina, Sousa Nuno, Almeida Osborne F X, Auer Dorothee P
NMR Research Group, Max Planck Institute of Psychiatry, Munich, Germany.
J Psychiatr Res. 2008 Sep;42(11):902-12. doi: 10.1016/j.jpsychires.2007.10.003. Epub 2008 Jan 3.
Altered corticosteroid milieu induces changes in hippocampal volume, neuronal structure, neurochemistry and cognitive function in humans and rodents. This in vivo magnetic resonance spectroscopy (1H MRS) and imaging (MRI) study investigated whether long-term alterations of the corticosteroid milieu cause: (i) metabolic and/or (ii) structural changes of the rat hippocampus. Therefore, hypocortisolism was induced by adrenalectomy (ADX), normocortisolism by ADX with low-dose corticosterone replacement, and hypercortisolism by ADX and high-dose dexamethasone treatment (for 11 weeks, respectively). All groups including a control group (n=23) were studied by in vivo 1H MRS and MR volumetry. Effects of treatment on normalized hippocampal metabolites and volumes were tested for significance using one-factorial multivariate analysis of variance (MANOVA). Hypercortisolemic rats revealed significantly elevated glutamate. Hypocortisolemic rats showed significantly decreased myo-inositol ratio levels, and were associated with significantly reduced normalized hippocampal volumes. Our findings suggest chronic hypercortisolism to be associated with glutamate-mediated excitotoxicity in the absence of volumetric abnormalities. In contrast, hypocortisolism appears to be associated with neurodegenerative processes, altered astrocytic metabolism but preserved neuronal density.
皮质类固醇环境的改变会在人类和啮齿动物中引起海马体体积、神经元结构、神经化学和认知功能的变化。这项体内磁共振波谱（1H MRS）和成像（MRI）研究调查了皮质类固醇环境的长期改变是否会导致：（i）大鼠海马体的代谢和/或（ii）结构变化。因此，通过肾上腺切除术（ADX）诱导低皮质醇血症，通过ADX加低剂量皮质酮替代诱导正常皮质醇血症，通过ADX和高剂量地塞米松治疗诱导高皮质醇血症（分别持续11周）。所有组包括一个对照组（n = 23）均通过体内1H MRS和磁共振体积测量法进行研究。使用单因素多变量方差分析（MANOVA）检验治疗对标准化海马体代谢物和体积的影响是否具有显著性。高皮质醇血症大鼠的谷氨酸水平显著升高。低皮质醇血症大鼠的肌醇比率水平显著降低，并且与标准化海马体体积显著减小有关。我们的研究结果表明，在没有体积异常的情况下，慢性高皮质醇血症与谷氨酸介导的兴奋性毒性有关。相比之下，低皮质醇血症似乎与神经退行性过程、星形胶质细胞代谢改变但神经元密度保持有关。
