IntroductionThe hippocampus is especially susceptible to age-associated neuronal pathologies, and there is concern that the age-associated rise in cortisol secretion from the adrenal gland may contribute to their etiology. Furthermore, because 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) catalyzes the reduction of cortisone to the active hormone cortisol, it is plausible that an increase in the expression of this enzyme enhances the deleterious impact of cortisol in the hippocampus and contributes to the neuronal pathologies that underlie cognitive decline in the elderly.MethodsRhesus macaques were used as a translational animal model of human aging, to examine age-related changes in gene and protein expressions of (HSD11B1/HSD11B1) in the hippocampus, a region of the brain that plays a crucial role in learning and memory.ResultsOlder animals showed significantly (p < 0.01) higher base-line cortisol levels in the circulation. In addition, they showed significantly (p < 0.05) higher hippocampal expression of HSD11B1 but not NR3C1 and NR3C2 (i.e., two receptor-encoding genes through which cortisol exerts its physiological actions). A similar age-related significant (p < 0.05) increase in the expression of the HSD11B1 was revealed at the protein level by western blot analysis.DiscussionThe data suggest that an age-related increase in the expression of hippocampal HSD11B1 is likely to raise cortisol concentrations in this cognitive brain area, and thereby contribute to the etiology of neuropathologies that ultimately lead to neuronal loss and dementia. Targeting this enzyme pharmacologically may help to reduce the negative impact of elevated cortisol concentrations within glucocorticoid-sensitive brain areas and thereby afford neuronal protection.

中文翻译：

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雄性恒河猴海马 1 型 11β-羟基类固醇脱氢酶表达与年龄相关的增加

简介海马体特别容易受到与年龄相关的神经元病变的影响，人们担心与年龄相关的肾上腺皮质醇分泌增加可能是其病因的原因之一。此外，由于 11β-羟基类固醇脱氢酶 1 型 (HSD11B1) 催化可的松还原为活性激素皮质醇，因此该酶表达的增加可能会增强海马中皮质醇的有害影响，并导致神经元病理学方法使用恒河猴作为人类衰老的转化动物模型，以检查与年龄相关的基因和蛋白质表达的变化（HSD11B1/HSD11B1）位于海马体中，海马体是大脑中在学习和记忆中起着至关重要作用的区域。结果老年动物表现出显着的（p< 0.01) 循环中基线皮质醇水平较高。此外，他们还表现出显着的（p< 0.05) 较高的海马表达HSD11B1但不是NR3C1和NR3C2（即，皮质醇通过两个受体编码基因发挥其生理作用）。类似的与年龄相关的显着（p< 0.05）通过蛋白质印迹分析在蛋白质水平上揭示了HSD11B1表达的增加。讨论数据表明海马表达的年龄相关增加HSD11B1可能会提高该认知脑区域的皮质醇浓度，从而导致神经病理学的病因学，最终导致神经元损失和痴呆。在药理学上靶向这种酶可能有助于减少糖皮质激素敏感大脑区域内皮质醇浓度升高的负面影响，从而提供神经元保护。