Meijer O C, Topic B, Steenbergen P J, Jocham G, Huston J P, Oitzl M S
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and Leiden University Medical Center, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
Endocrinology. 2005 Mar;146(3):1372-81. doi: 10.1210/en.2004-0416. Epub 2004 Nov 24.
Glucocorticoid hormones are released after activation of the hypothalamus-pituitary-adrenal (HPA) axis and in the brain can modulate synaptic plasticity and memory formation. Clear individual differences in spatial learning and memory in the water maze allowed classification of groups of young (3 months) and aged (24 months) male Wistar rats as superior and inferior learners. We tested 1) whether measures of HPA activity are associated with cognitive functions and aging and 2) whether correlations of these measures depend on age and learning performance. Basal ACTH, but not corticosterone, was increased in aged rats, with the stress-induced ACTH response exaggerated in aged-inferior learners. Aged-superior learners had lower expression of glucocorticoid receptor and CRH mRNA in the parvocellular paraventricular nucleus of the hypothalamus compared with all other groups. Hippocampal mineralocorticoid receptor and glucocorticoid receptor mRNAs differed modestly between groups, but steroid receptor coactivator and heat-shock-protein 90 mRNAs were not different. Strikingly, correlations between HPA axis markers were dependent on grouping animals according to learning performance or age. CRH mRNA correlated with ACTH only in aged animals. Parvocellular arginine vasopressin mRNA was negatively correlated to basal corticosterone, except in aged-inferior learners. Corticosteroid receptor mRNA expression showed a number of correlations with other HPA axis regulators specifically in superior learners. In summary, the relationships between HPA axis markers differ for subgroups of animals. These distinct interdependencies may reflect adjusted set-points of the HPA axis, resulting in adaptation (or maladaptation) to the environment and, possibly, an age-independent determination of learning ability.
下丘脑-垂体-肾上腺（HPA）轴激活后会释放糖皮质激素，其在大脑中可调节突触可塑性和记忆形成。水迷宫实验中空间学习和记忆存在明显个体差异，据此可将年轻（3个月）和老年（24个月）雄性Wistar大鼠分为优秀学习者和较差学习者两组。我们测试了：1）HPA活性指标是否与认知功能及衰老相关；2）这些指标的相关性是否取决于年龄和学习表现。老年大鼠基础促肾上腺皮质激素（ACTH）升高，而皮质酮未升高，且老年较差学习者应激诱导的ACTH反应增强。与其他所有组相比，老年优秀学习者下丘脑小细胞室旁核中糖皮质激素受体和促肾上腺皮质激素释放激素（CRH）mRNA表达较低。各组间海马盐皮质激素受体和糖皮质激素受体mRNA略有差异，但类固醇受体辅激活因子和热休克蛋白90 mRNA无差异。引人注目的是，HPA轴标志物之间的相关性取决于根据学习表现或年龄对动物进行分组。CRH mRNA仅在老年动物中与ACTH相关。除老年较差学习者外，小细胞精氨酸加压素mRNA与基础皮质酮呈负相关。皮质类固醇受体mRNA表达与其他HPA轴调节因子在优秀学习者中存在多种相关性。总之，HPA轴标志物之间的关系在动物亚组中有所不同。这些独特的相互依赖性可能反映了HPA轴设定点的调整，导致对环境的适应（或适应不良），并可能在不依赖年龄的情况下决定学习能力。
